Welcome to OPTIMA: The EPSRC and MRC Centre for Doctoral Training in Optical Medical Imaging

What is OPTIMA?

OPTIMA is a 4 year PhD training programme combining:

  • excellent research and PhD supervision in world-leading scientific environments, and
  • a bespoke programme of business training in healthcare innovation and entrepreneurship.

It is a Centre for Doctoral Training (CDT) funded by both the EPSRC and the MRC in recognition for our use of cutting-edge optical technology to address key clinical questions via medical imaging.

OPTIMA is hosted by the University of Edinburgh and the University of Strathclyde.

Our focus is to train the next generation of scientific entrepreneurs in healthcare technologies and so we place great emphasis on interdisciplinary projects, commercially-relevant training and strong ties to the clinical environment.

People

The key to OPTIMA’s success is its people.
Management, supervisors and students are working together to create a unique training environment

Management

OPTIMA's managment team are committed to delivering the best training possible for our students. Not only does it contain key leaders in the various academic fields represented by OPTIMA, but also a dedicated support staff of manager, outreach officer and administrators.

Meet the team behind OPTIMA...

Prof Mark Bradley

#####Principal Investigator

Over the past 7 or 8 years I, along with Dr Kev Dhaliwal, have established a centre for excellence in Optical Medical Imaging in Scotland. For example we run an EPSRC-funded Interdisciplinary Research Collaboration aimed at developing a Multiplexed "Touch and Tell" Optical Molecular Sensing and Imaging System. This system will provide real healthcare benefits for patients; as it uses optical imaging to allow doctors to rapidly diagnose patients and monitor them in real-time without the need for cumbersome equipment. In working on this programme it became clear that there was a national need to establish a Centre for Doctoral Training in Optical Medical Imaging to train the next generation of young researchers. However my vision goes beyond this. I am a strong believer in the rapid translation and application of my research - I have spun out 4 companies so far including an imaging company. And so OPTIMA is a product of what I see as an unmet need in the training of young scientists : all students will have a clinical focus while being driven by the cutting-edge technology of the physical sciences and at the same time receive a full year's worth of business training in entrepreneurship.

Prof Duncan Graham

#####Principal Investigator

Optical medical imaging is most certainly an area of growth in terms of research into new techniques and their applications. Translating this research into benefits to healthcare treatment is happening but to ensure this is occurs rapidly and is sustained we need to provide the next generation of highly skilled and innovative scientists and clinicians. OPTIMA was created with this view in mind and being involved with such a vibrant, dynamic and high quality doctoral training centre is something I find very exciting and rewarding.

Dr Colin Campbell

#####Director

As the Director my role has been to design and establish the training program that is an integral part of the CDT. I think that we’ve put together a program that’s really exciting and I would love to do if I was a student all over again.
Optical Medical Imaging is exciting and it’s also challenging I think we’ve put together a CDT that offers exciting research opportunities along with the support required to succeed in a multidisciplinary environment.

Prof Karen Faulds

#####Deputy Director

OPTIMA is an amazing opportunity to be involved in cutting edge research in optical medical imaging. The multidisciplinary ethos of the CDT and the exciting opportunities made available by being able to collaborate with biomedical scientists and clinicians to design innovative research projects with real world applications is truly unique. The students involved in the programme are all very motivated and engaged and I believe this is a great opportunity for them to carry out research in a truly multidisciplinary environment.

#####Principal Investigator

Over the past 7 or 8 years I, along with Dr Kev Dhaliwal, have established a centre for excellence in Optical Medical Imaging in Scotland. For example we run an EPSRC-funded Interdisciplinary Research Collaboration aimed at developing a Multiplexed "Touch and Tell" Optical Molecular Sensing and Imaging System. This system will provide real healthcare benefits for patients; as it uses optical imaging to allow doctors to rapidly diagnose patients and monitor them in real-time without the need for cumbersome equipment. In working on this programme it became clear that there was a national need to establish a Centre for Doctoral Training in Optical Medical Imaging to train the next generation of young researchers. However my vision goes beyond this. I am a strong believer in the rapid translation and application of my research - I have spun out 4 companies so far including an imaging company. And so OPTIMA is a product of what I see as an unmet need in the training of young scientists : all students will have a clinical focus while being driven by the cutting-edge technology of the physical sciences and at the same time receive a full year's worth of business training in entrepreneurship.

#####Principal Investigator

Optical medical imaging is most certainly an area of growth in terms of research into new techniques and their applications. Translating this research into benefits to healthcare treatment is happening but to ensure this is occurs rapidly and is sustained we need to provide the next generation of highly skilled and innovative scientists and clinicians. OPTIMA was created with this view in mind and being involved with such a vibrant, dynamic and high quality doctoral training centre is something I find very exciting and rewarding.

#####Director

As the Director my role has been to design and establish the training program that is an integral part of the CDT. I think that we’ve put together a program that’s really exciting and I would love to do if I was a student all over again.
Optical Medical Imaging is exciting and it’s also challenging I think we’ve put together a CDT that offers exciting research opportunities along with the support required to succeed in a multidisciplinary environment.

#####Deputy Director

OPTIMA is an amazing opportunity to be involved in cutting edge research in optical medical imaging. The multidisciplinary ethos of the CDT and the exciting opportunities made available by being able to collaborate with biomedical scientists and clinicians to design innovative research projects with real world applications is truly unique. The students involved in the programme are all very motivated and engaged and I believe this is a great opportunity for them to carry out research in a truly multidisciplinary environment.

Prof Kev Dhaliwal

#####Deputy Director

I am involved with OPTIMA because I am passionate about innovating in healthcare. Optical imaging will revolutionize modern healthcare by providing point of care molecular sensing and monitoring tools.. I see OPTIMA as an essential training ground for the College of Medicine & Veterinary Medicine to foster the future leaders in this area. Interdisciplinary research is the future of science. I work both as a consultant physician in the NHS and a University Senior Lecturer and my role in OPTIMA is to help provide the clinical bridge to optical imaging. I also wish to encourage young clinicians to embrace interdisciplinary research and join OPTIMA thorough clinical fellowships. We need to ‘light up disease’ and push molecular imaging into a new optical frontier.

Prof Chris Gregory

#####Deputy Director

The ability to visualize cell and tissue processes with high resolution lies at the heart of biomedical science. The reason I undertook an academic career in this field was a fascination with the microscopic world which inspired me from the very first time I looked down a light microscope in a biology class at school. Seeing is believing and optical imaging-based observation is a fundamentally powerful discovery tool for biological and medical science. The particular attraction of OPTIMA is that it uniquely provides new opportunities for such discovery by bringing true multidisciplinary expertise together. Successful multidisciplinary interactions are essential in 21st century biomedical research but are difficult to achieve. OPTIMA is successfully training the next generation of optical imaging scientists through just such interactions. That’s why it’s both satisfying and fun to be involved.

Prof Jamie Fleck

#####Deputy Director

As the representative from the University of Edinburgh Business School, I am leading on overseeing and delivering the innovation and enterprise elements of the OPTIMA programme. With nearly 40 years (!!) of involvement in research on science and high technology based innovation and entrepreneurship, I am really excited by the potential offered by the programme to go far beyond the normal bounds of PhD study, by making a substantial difference to the well being of society as well as providing an early lift off for a meteoric career for the participants.

Dr Jean O'Donoghue

#####Project Manager

To me, OPTIMA represents an amazing opportunity to transform PhD training. In funding this CDT, the EPSRC and the MRC have given us a responsibility and a challenge - to enshrine the value of interdisciplinary research from the beginning of our students' scientific careers and to enhance their training opportunities in order to meet the need for business-ready scientists in the future. My role in the team to make sure we are successful in our goal of "training the next generation of scientific entrepreneurs". I need to ensure our students our supported and encouraged through their training - as it is challenging combining research between lab groups/disciplines as well as participating in the integrated study modules. I also scope opportunities to improve our training in terms of making further connections outside OPTIMA with the commercial world, other CDTs and training professionals. If we do our job well - I hope OPTIMA can become a model for how PhD-training could be for all students in the future - challenging yet supportive - interdiscipinary yet focussed.

#####Deputy Director

I am involved with OPTIMA because I am passionate about innovating in healthcare. Optical imaging will revolutionize modern healthcare by providing point of care molecular sensing and monitoring tools.. I see OPTIMA as an essential training ground for the College of Medicine & Veterinary Medicine to foster the future leaders in this area. Interdisciplinary research is the future of science. I work both as a consultant physician in the NHS and a University Senior Lecturer and my role in OPTIMA is to help provide the clinical bridge to optical imaging. I also wish to encourage young clinicians to embrace interdisciplinary research and join OPTIMA thorough clinical fellowships. We need to ‘light up disease’ and push molecular imaging into a new optical frontier.

#####Deputy Director

The ability to visualize cell and tissue processes with high resolution lies at the heart of biomedical science. The reason I undertook an academic career in this field was a fascination with the microscopic world which inspired me from the very first time I looked down a light microscope in a biology class at school. Seeing is believing and optical imaging-based observation is a fundamentally powerful discovery tool for biological and medical science. The particular attraction of OPTIMA is that it uniquely provides new opportunities for such discovery by bringing true multidisciplinary expertise together. Successful multidisciplinary interactions are essential in 21st century biomedical research but are difficult to achieve. OPTIMA is successfully training the next generation of optical imaging scientists through just such interactions. That’s why it’s both satisfying and fun to be involved.

#####Deputy Director

As the representative from the University of Edinburgh Business School, I am leading on overseeing and delivering the innovation and enterprise elements of the OPTIMA programme. With nearly 40 years (!!) of involvement in research on science and high technology based innovation and entrepreneurship, I am really excited by the potential offered by the programme to go far beyond the normal bounds of PhD study, by making a substantial difference to the well being of society as well as providing an early lift off for a meteoric career for the participants.

#####Project Manager

To me, OPTIMA represents an amazing opportunity to transform PhD training. In funding this CDT, the EPSRC and the MRC have given us a responsibility and a challenge - to enshrine the value of interdisciplinary research from the beginning of our students' scientific careers and to enhance their training opportunities in order to meet the need for business-ready scientists in the future. My role in the team to make sure we are successful in our goal of "training the next generation of scientific entrepreneurs". I need to ensure our students our supported and encouraged through their training - as it is challenging combining research between lab groups/disciplines as well as participating in the integrated study modules. I also scope opportunities to improve our training in terms of making further connections outside OPTIMA with the commercial world, other CDTs and training professionals. If we do our job well - I hope OPTIMA can become a model for how PhD-training could be for all students in the future - challenging yet supportive - interdiscipinary yet focussed.

Dr Kirsty Ross

Outreach Officer

My scientific background in microbiology and immunology, as well as six years experience in public engagement, is enabling me to hit the ground running in the role of Outreach Officer. I was absolutely delighted to join OPTIMA's dynamic and enthusiastic team. It offers a unique opportunity to fuse industry engagement with community outreach. In this role, I hope to focus on reaching audiences who wouldn’t ordinarily get the opportunity to meet researchers in such a cutting-edge field, strengthening links with current industrial partners and forging new partnerships. Nanoscience and nanotechnology have the potential to revolutionise medicine and many other fields. By embedding engagement with end users from the start, it will be possible to address any concerns using open and honest dialogue and share the excitement! I am open to any and all ideas for how we could work together, so please do not hesitate to get in touch!

Mrs Samantha Brown

#####OPTIMA Administrator (Edinburgh)

I am the administrator on the OPTIMA project supporting staff and students in the University of Edinburgh. I manage and organise the student administration for the project, ensuring details of students, courses and programmes are stored accurately on the University system. I organise events, for example, summer schools and induction. A large part of my role is to monitor all financial related aspects of the project and ensure expenses and other financial related matters are processed timeously and efficiently. I liaise with applicants regarding their applications and interview arrangements and manage the logistics of organising the interviews.

Ms Gillian Neeson

#####OPTIMA Administrator (Strathclyde)

My role in OPTIMA includes providing full organisational and administrative support to the PI, Centre Director and Management Team. This includes production of a mid-term funding review, contribution to funding application processes, complex budget administration, development of best practice models including drafting, establishing and maintaining standard operating procedures, managing student recruitment, industrial placements and external promotion activities where appropriate, organisation of meetings, classes and workshops, collating and producing learning support materials, attending committees as appropriate and general administrative duties.

Outreach Officer

My scientific background in microbiology and immunology, as well as six years experience in public engagement, is enabling me to hit the ground running in the role of Outreach Officer. I was absolutely delighted to join OPTIMA's dynamic and enthusiastic team. It offers a unique opportunity to fuse industry engagement with community outreach. In this role, I hope to focus on reaching audiences who wouldn’t ordinarily get the opportunity to meet researchers in such a cutting-edge field, strengthening links with current industrial partners and forging new partnerships. Nanoscience and nanotechnology have the potential to revolutionise medicine and many other fields. By embedding engagement with end users from the start, it will be possible to address any concerns using open and honest dialogue and share the excitement! I am open to any and all ideas for how we could work together, so please do not hesitate to get in touch!

#####OPTIMA Administrator (Edinburgh)

I am the administrator on the OPTIMA project supporting staff and students in the University of Edinburgh. I manage and organise the student administration for the project, ensuring details of students, courses and programmes are stored accurately on the University system. I organise events, for example, summer schools and induction. A large part of my role is to monitor all financial related aspects of the project and ensure expenses and other financial related matters are processed timeously and efficiently. I liaise with applicants regarding their applications and interview arrangements and manage the logistics of organising the interviews.

#####OPTIMA Administrator (Strathclyde)

My role in OPTIMA includes providing full organisational and administrative support to the PI, Centre Director and Management Team. This includes production of a mid-term funding review, contribution to funding application processes, complex budget administration, development of best practice models including drafting, establishing and maintaining standard operating procedures, managing student recruitment, industrial placements and external promotion activities where appropriate, organisation of meetings, classes and workshops, collating and producing learning support materials, attending committees as appropriate and general administrative duties.

Supervisors

OPTIMA brings together two internationally leading teams. The combination of capabilities in physical sciences and clinical translation offered through this partnership present an unsurpassed environment for dynamic postgraduate training.

Our team of supervisors is of international standing in their respective fields. They have published in excess of 1300 peer-reviewed papers, are in receipt of research grant income in excess of £110M and have supervised in excess of 300 PhD students.

Prof Alison Hulme

######School of Chemistry, University of Edinburgh

My research interests in natural products chemistry cover diverse fields, from synthetic organic chemistry and chemical biology and medicine, to imaging and historic textile dyestuffs. I have a particular interest in the synthesis of natural products which interact with their biological targets through several, or many, chiral groups. We use libraries based around these natural product targets to investigate their structure activity relationships. I’m also interested in the design and synthesis of small molecule probes to investigate the interactions of biomolecules both in vivo and in vitro. We use a range of techniques (affinity chromatography, FRET, NMR footprinting, MS, Raman spectroscopy etc.) to investigate how our natural products and other biomolecules such as glycosaminoglycans, steroids and peptide aptamers bind to their cellular targets.

Dr Alastair Wark

######Department of Pure and Applied Chemistry, University of Strathclyde

My research focus is based around the synthesis, functionalization and analytical applications of novel nanomaterials alongside the development of techniques capable of optically imaging and tracking single nanoparticles and molecules. The advantages of these materials for nanometrology and bioanalytical science is that optical measurements can be performed to monitor biomolecular interactions in real-time. As well as developing robust methodologies for ultrasensitive bioaffinity detection at target concentrations approaching just a few molecules, we are also exploring the use of multimodal imaging techniques for monitoring nanoparticle-cellular interactions. This involves developing hybrid nanostructures which can be used for tackling research challenges requiring dynamic measurements in complex biological environments. Consequently, my research is highly multidisciplinary and I have enjoyed successfully collaborating with researchers from across the biology, physics, engineering and medicine research fields.

Dr Andy Downes

######School of Engineering, University of Edinburgh

My research is focussed on label-free optical imaging and spectroscopy, applied to living cells and tissue. Label-free optical techniques are ideally suited to distinguishing cancerous from healthy cells. These fall into three categories: molecular bond vibrations (Raman), second harmonic generation (collagen), and autofluorescence (elastin).

Prof David Birch

######Department of Physics, University of Strathclyde

My group focuses on interdisciplinary molecular grand challenges at the biomedical interface that are relevant to metabolism and disease. We are among the pioneers of modern-day fluorescence lifetime spectroscopy and the initiators and driving force behind Scotland being the global manufacturing hub for fluorescence lifetime instrumentation. Many of the techniques and instrumentation first published by the group are now in widespread use and are standards in the field. For example, multiplexed time-correlated single-photon counting has become the method of choice for fluorescence lifetime imaging (FLIM). Current research includes biomolecular structure and dynamics down to the single molecule level, melanin structure, photophysics and melanoma; glucose sensing for diabetes; aggregation leading to fibrils e.g. beta-amyloid and Alzheimer’s disease; gold nanoparticle photophysics and its application to sensing and imaging; and 1-10 nm silica nanoparticle metrology.

######School of Chemistry, University of Edinburgh

My research interests in natural products chemistry cover diverse fields, from synthetic organic chemistry and chemical biology and medicine, to imaging and historic textile dyestuffs. I have a particular interest in the synthesis of natural products which interact with their biological targets through several, or many, chiral groups. We use libraries based around these natural product targets to investigate their structure activity relationships. I’m also interested in the design and synthesis of small molecule probes to investigate the interactions of biomolecules both in vivo and in vitro. We use a range of techniques (affinity chromatography, FRET, NMR footprinting, MS, Raman spectroscopy etc.) to investigate how our natural products and other biomolecules such as glycosaminoglycans, steroids and peptide aptamers bind to their cellular targets.

######Department of Pure and Applied Chemistry, University of Strathclyde

My research focus is based around the synthesis, functionalization and analytical applications of novel nanomaterials alongside the development of techniques capable of optically imaging and tracking single nanoparticles and molecules. The advantages of these materials for nanometrology and bioanalytical science is that optical measurements can be performed to monitor biomolecular interactions in real-time. As well as developing robust methodologies for ultrasensitive bioaffinity detection at target concentrations approaching just a few molecules, we are also exploring the use of multimodal imaging techniques for monitoring nanoparticle-cellular interactions. This involves developing hybrid nanostructures which can be used for tackling research challenges requiring dynamic measurements in complex biological environments. Consequently, my research is highly multidisciplinary and I have enjoyed successfully collaborating with researchers from across the biology, physics, engineering and medicine research fields.

######School of Engineering, University of Edinburgh

My research is focussed on label-free optical imaging and spectroscopy, applied to living cells and tissue. Label-free optical techniques are ideally suited to distinguishing cancerous from healthy cells. These fall into three categories: molecular bond vibrations (Raman), second harmonic generation (collagen), and autofluorescence (elastin).

######Department of Physics, University of Strathclyde

My group focuses on interdisciplinary molecular grand challenges at the biomedical interface that are relevant to metabolism and disease. We are among the pioneers of modern-day fluorescence lifetime spectroscopy and the initiators and driving force behind Scotland being the global manufacturing hub for fluorescence lifetime instrumentation. Many of the techniques and instrumentation first published by the group are now in widespread use and are standards in the field. For example, multiplexed time-correlated single-photon counting has become the method of choice for fluorescence lifetime imaging (FLIM). Current research includes biomolecular structure and dynamics down to the single molecule level, melanin structure, photophysics and melanoma; glucose sensing for diabetes; aggregation leading to fibrils e.g. beta-amyloid and Alzheimer’s disease; gold nanoparticle photophysics and its application to sensing and imaging; and 1-10 nm silica nanoparticle metrology.

Prof Charles ffrench-Constant

######Centre for Regenerative Medicine, University of Edinburgh

The principal focus of our research is multiple sclerosis (MS), an inflammatory progressive disease in which the myelin around the axons of the central nervous system (CNS) is damaged. We identify molecules and signalling pathways that can be used to enhance repair in the damaged CNS by recruiting stem cells and by enhancing the formation of myelin sheaths by the new oligodendrocytes formed by these stem cells. Additionally, ongoing collaborative projects in our laboratory also address spinal-cord injury.
The CNS consists of the brain and the spinal cord and is made up of nerve cells (neurons) and glial cells. The neurons transmit information from one cell to another, while the glial cells support and protect the neurons. Oligodendrocytes, one of the supporting glial cell types, form the myelin that insulates the axons of neurons. These cells are damaged in MS, and can be replaced by new oligodendrocytes formed by stem cell-like oligodendrocyte precursors. In MS this repair fails, and overcoming this failure is the focus of our research with specific goals being i) the mechanisms by which oligodendrocytes form a myelin sheath and ii) how the stem cells in the CNS become activated to contribute to oligodendrocyte replacement.

Prof Chris Haslett

######Centre for Inflammation Research, University of Edinburgh

Early in my career my focus was on harnessing the apoptotic and recognition processes to drive resolution of inflammation/scarring processes culminating in the key discovery that cdk inhibitors could 'drive' neutrophil apoptosis and promote the resolution of inflammatory/scarring processes. In the past five years I have joined forces with Mark Bradley and Kev Dhaliwal to create novel optical imaging 'smartprobes' which, partnered by in vivo bronchoscopic confocal microscopy, are now ready for 'first-into-man' application in lung inflammation fibrosis. The discovery of granulocyte apoptosis and the recognition of its likely role in the pathogenesis of inflammatory disease has stimulated research in this field in many laboratories internationally. The recent demonstration that it can be harnessed for potential benefit provides a new approach to the treatment of currently intractable inflammatory diseases of the lung and other organs. There is considerable interest in our new optical imaging approach to detecting 'real-time' specific molecular events deep in diseased human tissues. This will provide novel tools for drug design, patient stratification and rapid assessment of drug efficacy.

Prof Alistair Elfick

######School of Engineering, University of Edinburgh

My research interests include:
Optical Spectroscopy – this is a very valuable tool for non-invasively probing the chemistry and molecular structure of matter. We are developing instrumentation to investigate the utility of conducting near-field optical microscopy and spectroscopy using an apertureless approach.
Orthopaedic biomaterials - research into the wear performance of total joint replacements. This work is augmented with investigation of the cellular/tissue reaction to orthopaedic biomaterials and their wear products.
Synthetic Biology - is an emergent discipline in which we undertake to rationally design and fabricate biological devices which show some desired functionality.
Nanotribology - the tribology of biological systems is in general poorly understood at the molecular level. On-going basic science research into the molecular lubricating ability of adsorbed proteins glycoproteins lipids polyelectrolytes and so on will inform many future medical and engineering applications.

Prof David Newby

######Centre for Cardiovascular Science, University of Edinburgh

My principal research interests are in endothelial and vascular biology, acute coronary syndromes and heart failure; focusing on clinical experimental and translational medicine. I currently hold a Programme Grant from the British Heart Foundation to explore the adverse cardiovascular effects of air pollution. I am involved in several multicentre trials and have played a major role in the conduct of the SALTIRE (Scottish Aortic stenosis Lipid lowering Trial, Impact on REgression) and 3CPO (Health Technology Assessment trial of non-invasive ventilation for acute cardiogenic pulmonary oedema) trials.

######Centre for Regenerative Medicine, University of Edinburgh

The principal focus of our research is multiple sclerosis (MS), an inflammatory progressive disease in which the myelin around the axons of the central nervous system (CNS) is damaged. We identify molecules and signalling pathways that can be used to enhance repair in the damaged CNS by recruiting stem cells and by enhancing the formation of myelin sheaths by the new oligodendrocytes formed by these stem cells. Additionally, ongoing collaborative projects in our laboratory also address spinal-cord injury.
The CNS consists of the brain and the spinal cord and is made up of nerve cells (neurons) and glial cells. The neurons transmit information from one cell to another, while the glial cells support and protect the neurons. Oligodendrocytes, one of the supporting glial cell types, form the myelin that insulates the axons of neurons. These cells are damaged in MS, and can be replaced by new oligodendrocytes formed by stem cell-like oligodendrocyte precursors. In MS this repair fails, and overcoming this failure is the focus of our research with specific goals being i) the mechanisms by which oligodendrocytes form a myelin sheath and ii) how the stem cells in the CNS become activated to contribute to oligodendrocyte replacement.

######Centre for Inflammation Research, University of Edinburgh

Early in my career my focus was on harnessing the apoptotic and recognition processes to drive resolution of inflammation/scarring processes culminating in the key discovery that cdk inhibitors could 'drive' neutrophil apoptosis and promote the resolution of inflammatory/scarring processes. In the past five years I have joined forces with Mark Bradley and Kev Dhaliwal to create novel optical imaging 'smartprobes' which, partnered by in vivo bronchoscopic confocal microscopy, are now ready for 'first-into-man' application in lung inflammation fibrosis. The discovery of granulocyte apoptosis and the recognition of its likely role in the pathogenesis of inflammatory disease has stimulated research in this field in many laboratories internationally. The recent demonstration that it can be harnessed for potential benefit provides a new approach to the treatment of currently intractable inflammatory diseases of the lung and other organs. There is considerable interest in our new optical imaging approach to detecting 'real-time' specific molecular events deep in diseased human tissues. This will provide novel tools for drug design, patient stratification and rapid assessment of drug efficacy.

######School of Engineering, University of Edinburgh

My research interests include:
Optical Spectroscopy – this is a very valuable tool for non-invasively probing the chemistry and molecular structure of matter. We are developing instrumentation to investigate the utility of conducting near-field optical microscopy and spectroscopy using an apertureless approach.
Orthopaedic biomaterials - research into the wear performance of total joint replacements. This work is augmented with investigation of the cellular/tissue reaction to orthopaedic biomaterials and their wear products.
Synthetic Biology - is an emergent discipline in which we undertake to rationally design and fabricate biological devices which show some desired functionality.
Nanotribology - the tribology of biological systems is in general poorly understood at the molecular level. On-going basic science research into the molecular lubricating ability of adsorbed proteins glycoproteins lipids polyelectrolytes and so on will inform many future medical and engineering applications.

######Centre for Cardiovascular Science, University of Edinburgh

My principal research interests are in endothelial and vascular biology, acute coronary syndromes and heart failure; focusing on clinical experimental and translational medicine. I currently hold a Programme Grant from the British Heart Foundation to explore the adverse cardiovascular effects of air pollution. I am involved in several multicentre trials and have played a major role in the conduct of the SALTIRE (Scottish Aortic stenosis Lipid lowering Trial, Impact on REgression) and 3CPO (Health Technology Assessment trial of non-invasive ventilation for acute cardiogenic pulmonary oedema) trials.

Dr Colin Campbell

######School of Chemistry, University of Edinburgh

My research direction is towards understanding the role of redox chemistry in biological systems. Understanding how redox chemistry impacts biological function is important because it not only underpins normal cell function, but when it goes wrong it is implicated in diseases ranging from neurodegeneration to cancer. This research has two distinct components: SERS nanosensors for measuring intracellular redox potential and mapping circuits of redox regulation in cells using systems-biology notation. SERS Nanosensors Gold nanoshells (metal-coated dielectrics) are a novel-class of optically-tuneable nanoparticle for which optical absorption can be controlled by adjusting the dimensions of the core and shell. This property can be exploited to design nanoparticles optimized for use in spectral regions where most biological materials are fairly transparent and exhibit low autofluorescence. We recently reported the first use of gold nanoshells as intracellular sensors based on surface-enhanced Raman scattering (SERS) and have since established that these materials exhibit low toxicity to the cells of interest. We are now actively developing sensors based on chemically modified nanoshells to measure redox potential in living cells.

Prof Sarah Walmsley

######MRC Centre for Inflammation Research, University of Edinburgh

To date there are no effective treatments for neutrophilic inflammation which is central to the pathology of a number of important respiratory diseases including COPD, bronchiectasis and ARDS. Neutrophils as key effectors of the innate immune response are required to function at sites of inflammation that are relatively oxygen deplete – hypoxic. Unique to the neutrophil hypoxia is a profound survival stimulus. Neutrophils both sense oxygen and respond to changes in oxygenation via the HIF pathway, which involves regulation of the transcription factor hypoxia inducible factor (HIF) by von Hippel Lindau protein and a group of oxygen sensitive hydroxylases – prolyl hydroxylase domain (PHD) containing enzymes and factor inhibiting HIF (FIH). Preliminary data suggest a direct role for this oxygen sensing pathway in the regulation of neutrophil apoptosis at sites of hypoxia. I aim to elucidate the mechanisms regulating HIF-1alpha expression in neutrophils and determine the importance of these pathways for neutrophilic inflammation in vivo.

Prof Jeffrey Pollard

######MRC Centre for Reproductive Health, University of Edinburgh

My main research interests focus on the understanding of the tumour microenvironment and the mechanisms of action of oestrogen and progesterone in controlling cell division in vivo. My research takes a comprehensive approach to studying these problems by using mouse genetics to dissect the molecular mechanisms in vivo. We also apply state of the art high throughput methods and novel in vivo imaging methods to define cellular interactions and the novel signalling pathways involved in these interactions. Another research emphasis includes examining the mechanisms of action of female sex steroid hormones in controlling cell proliferation and on the tumour microenvironment of breast cancer. In the former programme my lab has sought to understand the mechanism of progesterone in negatively regulating oestrogen-induced uterine epithelial cell proliferation and in the preparation of the uterus for blastocyst implantation. In the latter area we have pioneered studies on the role of macrophages and demonstrated that they promote tumour progression and malignancy. Our work has focused upon mechanisms behind these pro-tumoural actions of macrophages with a particular emphasis on metastatic disease.

Prof Chris Gregory

######MRC Centre of Inflammation Research, University of Edinburgh
High-grade cancers often contain large numbers of dying tumour cells alongside those that proliferate, the balance of cell-birth versus cell-death favouring net tumour growth. We believe that different categories of normal white blood cells ‘sense' these dying cells and are either attracted to the tumours to help them to grow or are excluded from the tumours to prevent their destruction. Our research will define the mechanisms by which white cells invade malignant tumours and aims to identify novel targets that may be used to treat cancers in the future by controlling their infiltration by normal blood cells and encouraging the dying cells in the tumour to activate the white blood cells to become tumour-destructive. Our understanding of how dead cells affect their viable neighbours will also help to improve the production of therapeutic cells and protein medicines in culture.

######School of Chemistry, University of Edinburgh

My research direction is towards understanding the role of redox chemistry in biological systems. Understanding how redox chemistry impacts biological function is important because it not only underpins normal cell function, but when it goes wrong it is implicated in diseases ranging from neurodegeneration to cancer. This research has two distinct components: SERS nanosensors for measuring intracellular redox potential and mapping circuits of redox regulation in cells using systems-biology notation. SERS Nanosensors Gold nanoshells (metal-coated dielectrics) are a novel-class of optically-tuneable nanoparticle for which optical absorption can be controlled by adjusting the dimensions of the core and shell. This property can be exploited to design nanoparticles optimized for use in spectral regions where most biological materials are fairly transparent and exhibit low autofluorescence. We recently reported the first use of gold nanoshells as intracellular sensors based on surface-enhanced Raman scattering (SERS) and have since established that these materials exhibit low toxicity to the cells of interest. We are now actively developing sensors based on chemically modified nanoshells to measure redox potential in living cells.

######MRC Centre for Inflammation Research, University of Edinburgh

To date there are no effective treatments for neutrophilic inflammation which is central to the pathology of a number of important respiratory diseases including COPD, bronchiectasis and ARDS. Neutrophils as key effectors of the innate immune response are required to function at sites of inflammation that are relatively oxygen deplete – hypoxic. Unique to the neutrophil hypoxia is a profound survival stimulus. Neutrophils both sense oxygen and respond to changes in oxygenation via the HIF pathway, which involves regulation of the transcription factor hypoxia inducible factor (HIF) by von Hippel Lindau protein and a group of oxygen sensitive hydroxylases – prolyl hydroxylase domain (PHD) containing enzymes and factor inhibiting HIF (FIH). Preliminary data suggest a direct role for this oxygen sensing pathway in the regulation of neutrophil apoptosis at sites of hypoxia. I aim to elucidate the mechanisms regulating HIF-1alpha expression in neutrophils and determine the importance of these pathways for neutrophilic inflammation in vivo.

######MRC Centre for Reproductive Health, University of Edinburgh

My main research interests focus on the understanding of the tumour microenvironment and the mechanisms of action of oestrogen and progesterone in controlling cell division in vivo. My research takes a comprehensive approach to studying these problems by using mouse genetics to dissect the molecular mechanisms in vivo. We also apply state of the art high throughput methods and novel in vivo imaging methods to define cellular interactions and the novel signalling pathways involved in these interactions. Another research emphasis includes examining the mechanisms of action of female sex steroid hormones in controlling cell proliferation and on the tumour microenvironment of breast cancer. In the former programme my lab has sought to understand the mechanism of progesterone in negatively regulating oestrogen-induced uterine epithelial cell proliferation and in the preparation of the uterus for blastocyst implantation. In the latter area we have pioneered studies on the role of macrophages and demonstrated that they promote tumour progression and malignancy. Our work has focused upon mechanisms behind these pro-tumoural actions of macrophages with a particular emphasis on metastatic disease.

######MRC Centre of Inflammation Research, University of Edinburgh
High-grade cancers often contain large numbers of dying tumour cells alongside those that proliferate, the balance of cell-birth versus cell-death favouring net tumour growth. We believe that different categories of normal white blood cells ‘sense' these dying cells and are either attracted to the tumours to help them to grow or are excluded from the tumours to prevent their destruction. Our research will define the mechanisms by which white cells invade malignant tumours and aims to identify novel targets that may be used to treat cancers in the future by controlling their infiltration by normal blood cells and encouraging the dying cells in the tumour to activate the white blood cells to become tumour-destructive. Our understanding of how dead cells affect their viable neighbours will also help to improve the production of therapeutic cells and protein medicines in culture.

Dr Gordon Flockhart

######Department of Electronic and Electrical Engineering, University of Strathclyde

I am a member of the Centre for Microsystems and Photonics and my research investigates the application of photonic technologies for measurement applications. Optical sensing technologies provide a range of different advantages compared to conventional electrical sensors. For some applications, these advantages allow optical sensors to provide a unique solution whereas conventional electrical sensors may not meet the required specification. I enjoy the challenge of developing optical sensing systems where photonics, electronics and software systems are integrated. As a researcher this exposes me to a wide range of technologies and the applications of my research can be quite varied from underwater acoustics to bio-medical applications.

Dr Yu Chen

######Department of Physics, University of Strathclyde

My main research activities lie in the creation and characterization of nanoscale structures for their unique physical and chemical properties, utilizing both optical and electron microscopy and spectroscopy. My recent research focuses on surface plasmon enhanced effect, including two-photon luminescence, energy transfer and SERRS from noble metal nanoparticles, arrays and porous media, with strong links to biomedical imaging and sensing, as well as nanoparticle-cell interaction and cytotoxicity. Other work includes 3D visualization of nanoparticles, stability of Au nanoparticles, and creating nanostructures using chemical lithography and direct writing.

Dr Carmel Moran

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

My research interests are in ultrasonic contrast agents and high frequency clinical and preclinical ultrasound imaging

Prof Deepak Uttamchandani

######Department of Electronic and Electrical Engineering, University of Strathclyde

Our research interests include:
• Fibre optic sensors for physical and chemical measurements
• Silicon micro-engineering for sensors
• Optoelectronic applications for silicon and doped glasses
• Nanometric resolution optical sensors
• Optical network studies including multiple access.

######Department of Electronic and Electrical Engineering, University of Strathclyde

I am a member of the Centre for Microsystems and Photonics and my research investigates the application of photonic technologies for measurement applications. Optical sensing technologies provide a range of different advantages compared to conventional electrical sensors. For some applications, these advantages allow optical sensors to provide a unique solution whereas conventional electrical sensors may not meet the required specification. I enjoy the challenge of developing optical sensing systems where photonics, electronics and software systems are integrated. As a researcher this exposes me to a wide range of technologies and the applications of my research can be quite varied from underwater acoustics to bio-medical applications.

######Department of Physics, University of Strathclyde

My main research activities lie in the creation and characterization of nanoscale structures for their unique physical and chemical properties, utilizing both optical and electron microscopy and spectroscopy. My recent research focuses on surface plasmon enhanced effect, including two-photon luminescence, energy transfer and SERRS from noble metal nanoparticles, arrays and porous media, with strong links to biomedical imaging and sensing, as well as nanoparticle-cell interaction and cytotoxicity. Other work includes 3D visualization of nanoparticles, stability of Au nanoparticles, and creating nanostructures using chemical lithography and direct writing.

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

My research interests are in ultrasonic contrast agents and high frequency clinical and preclinical ultrasound imaging

######Department of Electronic and Electrical Engineering, University of Strathclyde

Our research interests include:
• Fibre optic sensors for physical and chemical measurements
• Silicon micro-engineering for sensors
• Optoelectronic applications for silicon and doped glasses
• Nanometric resolution optical sensors
• Optical network studies including multiple access.

Dr Alan Serrels

######Institute of Genetics and Molecular Medicine, Univeristy of Edinburgh

The tumour is a complex ‘organ’ consisting of many cell types that interact to support tumour growth and drive metastasis. In order to try and understanding how tumour cells interact with their surrounding microenvironment and better characterize the role of integrin signalling in this context, we use intra-vital imaging to see with great detail phenotypic changes in both tumour cell behaviour and the microenvironment when we perturb signalling either through mutagenesis, gene knockout, or treatment with pharmacological inhibitors. Using advanced microscopy techniques such as confocal, multi-photon, FLIM, FRAP, photo-activation, photo-switching, and vibrational spectroscopy, we have performed ‘in vivo phenotypic profiling’ of the role of FAK in cancer biology, and in collaboration with the labs of Professor Margaret Frame and Dr Bryan Serrels are using pathway analysis and proteomics to interrogate the signalling underlying these phenotypes in order to identify new therapeutic targets.

Continued development and application of advanced microscopy techniques to in vivo cancer research is a key aim of our lab as we aim to derive a greater degree of information from a single sample. In search of this goal we have recently built and continue to develop (in collaboration with Dr Andy Downes) a bespoke multi-modal microscope that combines two-photon fluorescence and Fluorescence Lifetime Imaging (FLIM), with label-free imaging modalities including Second Harmonic Generation (SHG), Coherent Anti-stokes Raman Scattering (CARS), and Stimulated Raman Scattering (SRS). This combinatorial approach offers great benefits over using just confocal or multi-photon microscopy on their own, by adding a greater degree of context and understanding to the image. In addition, the potential to use CARS and SRS for imaging anti-cancer drugs is still under investigation, and is the focus of a collaboration with the labs of Professor Margaret Frame, Professor Val Brunton, and Dr Alison Hulme.

Prof Karen Faulds

######Department of Pure and Applied Chemistry, University of Strathclyde

Our research focuses on using surface enhanced Raman scattering (SERS) to create new approaches to bioanalysis for use in the life and clinical sciences. SERS is a spectroscopic technique that offers significant advantages over other established techniques such as fluorescence and our research has focused on highlighting the advantages, creating new examples of increased capability in life science applications and interacting with end users to shape future step changes in research. Our research centres around using the inherent sensitivity of SERS for the detection of target DNA or proteins using signal amplification methods to enhance the signal rather than using target amplification methods such as PCR. Our work has focussed on exploiting the sensitivity of SERS for quantitative analysis of biomolecules as well as exploiting one of the key advantages of SERS, the ability to analyse multiple analytes in one sample. This allows more information to be gained per analysis as well as giving information about complex systems that are intrinsically difficult to measure.

Dr Fabio Nudelman

######School of Chemistry, University of Edinburgh

We are interested in understanding how organisms produce mineralized tissues like bone, teeth and shells. These tissues are organic-inorganic composite materials, where the formation of the inorganic phase is controlled by a matrix of proteins and polysaccharides that compose the organic phase. The intimate relationship between the organic and inorganic phases results in materials that are highly adapted for their functions.

Prof Robert Henderson

######School of Engineering, University of Edinburgh

My research interests include :

CMOS Image Sensors
Column-parallel and pixel-parallel ADC structures, fixed-pattern noise reduction, low-noise readout architectures, pixel structures, high-speed imagers, 3D imaging, kTC noise reduction
Mixed-signal CMOS Integrated Circuit Design
ADC architectures (flash, pipeline, cyclic, sigma-delta, successive etc), DACs, PLLs, DLLs, bandgaps, filters.

Sigma-delta ADC and DACs
Low-power, low-voltage architectures, multi-bit DAC linearization, high-sample rate, switched-capacitor and continuous-time implementations
Biosensors
Fluorescence detection, dielectrophoresis, chemical sensing, lab-on-a-chip

######Institute of Genetics and Molecular Medicine, Univeristy of Edinburgh

The tumour is a complex ‘organ’ consisting of many cell types that interact to support tumour growth and drive metastasis. In order to try and understanding how tumour cells interact with their surrounding microenvironment and better characterize the role of integrin signalling in this context, we use intra-vital imaging to see with great detail phenotypic changes in both tumour cell behaviour and the microenvironment when we perturb signalling either through mutagenesis, gene knockout, or treatment with pharmacological inhibitors. Using advanced microscopy techniques such as confocal, multi-photon, FLIM, FRAP, photo-activation, photo-switching, and vibrational spectroscopy, we have performed ‘in vivo phenotypic profiling’ of the role of FAK in cancer biology, and in collaboration with the labs of Professor Margaret Frame and Dr Bryan Serrels are using pathway analysis and proteomics to interrogate the signalling underlying these phenotypes in order to identify new therapeutic targets.

Continued development and application of advanced microscopy techniques to in vivo cancer research is a key aim of our lab as we aim to derive a greater degree of information from a single sample. In search of this goal we have recently built and continue to develop (in collaboration with Dr Andy Downes) a bespoke multi-modal microscope that combines two-photon fluorescence and Fluorescence Lifetime Imaging (FLIM), with label-free imaging modalities including Second Harmonic Generation (SHG), Coherent Anti-stokes Raman Scattering (CARS), and Stimulated Raman Scattering (SRS). This combinatorial approach offers great benefits over using just confocal or multi-photon microscopy on their own, by adding a greater degree of context and understanding to the image. In addition, the potential to use CARS and SRS for imaging anti-cancer drugs is still under investigation, and is the focus of a collaboration with the labs of Professor Margaret Frame, Professor Val Brunton, and Dr Alison Hulme.

######Department of Pure and Applied Chemistry, University of Strathclyde

Our research focuses on using surface enhanced Raman scattering (SERS) to create new approaches to bioanalysis for use in the life and clinical sciences. SERS is a spectroscopic technique that offers significant advantages over other established techniques such as fluorescence and our research has focused on highlighting the advantages, creating new examples of increased capability in life science applications and interacting with end users to shape future step changes in research. Our research centres around using the inherent sensitivity of SERS for the detection of target DNA or proteins using signal amplification methods to enhance the signal rather than using target amplification methods such as PCR. Our work has focussed on exploiting the sensitivity of SERS for quantitative analysis of biomolecules as well as exploiting one of the key advantages of SERS, the ability to analyse multiple analytes in one sample. This allows more information to be gained per analysis as well as giving information about complex systems that are intrinsically difficult to measure.

######School of Chemistry, University of Edinburgh

We are interested in understanding how organisms produce mineralized tissues like bone, teeth and shells. These tissues are organic-inorganic composite materials, where the formation of the inorganic phase is controlled by a matrix of proteins and polysaccharides that compose the organic phase. The intimate relationship between the organic and inorganic phases results in materials that are highly adapted for their functions.

######School of Engineering, University of Edinburgh

My research interests include :

CMOS Image Sensors
Column-parallel and pixel-parallel ADC structures, fixed-pattern noise reduction, low-noise readout architectures, pixel structures, high-speed imagers, 3D imaging, kTC noise reduction
Mixed-signal CMOS Integrated Circuit Design
ADC architectures (flash, pipeline, cyclic, sigma-delta, successive etc), DACs, PLLs, DLLs, bandgaps, filters.

Sigma-delta ADC and DACs
Low-power, low-voltage architectures, multi-bit DAC linearization, high-sample rate, switched-capacitor and continuous-time implementations
Biosensors
Fluorescence detection, dielectrophoresis, chemical sensing, lab-on-a-chip

Prof Duncan Graham

######Department of Pure and Applied Chemistry, University of Strathclyde

The main focus of my work is the creation of a range of functionalised metallic nanoparticles which can be used for a variety of different purposes which include the diagnosis of disease and also the treatment of disease. This includes the chemical manipulation of the appropriate surface molecules and labels required to turn these metal nanoparticles into functioning nanosensors capable of detecting single molecules in complex environments using SERS (Surface Enhanced Raman Spectroscopy). In addition, the mounting of therapeutic agents onto these nanoparticles has resulted in significantly increased performance of the drugs when tested against particular disease states.

Prof John Mullins

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

My research interests focus on the molecular mechanisms of blood pressure regulation and in particular the genetics of the renin-angiotensin-aldosterone system.

Prof Peter Brophy

######Centre for Neuroregeneration, University of Edinburgh

In the developing vertebrate nervous system, oligodendrocytes and Schwann cells not only play a vital role in promoting neuron survival, but
they also produce the myelin sheath, which is essential for the normal function of the nervous system, a fact underscored by the debilitating consequences of demyelination in multiple sclerosis (CNS) and in peripheral neuropathies of the Charcot-Marie-Tooth (PNS) type. In one project we are building on our discovery of the Periaxin (Prx) gene in Schwann cells. Mice lacking a functional Prx gene ensheath and myelinate peripheral nerve axons in an apparently normal manner but the sheath later destabilizes and the mice develop a severe demyelinating neuropathy. In collaboration with colleagues in Paris we have identified a human disease called CMT-4F caused by similar mutations. In a second project, we have shown that two isoforms of neurofascin, one glial, the other neuronal, play distinct but vital roles in the assembly of the node of Ranvier. The role of these proteins during both normal development and during nerve repair is the subject of current work.

Dr James Hopgood

######School of Engineering, University of Edinburgh

My research specialisation include model-based Bayesian signal processing, speech and audio signal processing in adverse acoustic environments, including blind dereverberation and multi-target acoustic source localisation and tracking, single channel signal separation, distant speech recognition, audio-visual fusion, medical imaging, blind image deconvolution, and general statistical signal and image processing.

######Department of Pure and Applied Chemistry, University of Strathclyde

The main focus of my work is the creation of a range of functionalised metallic nanoparticles which can be used for a variety of different purposes which include the diagnosis of disease and also the treatment of disease. This includes the chemical manipulation of the appropriate surface molecules and labels required to turn these metal nanoparticles into functioning nanosensors capable of detecting single molecules in complex environments using SERS (Surface Enhanced Raman Spectroscopy). In addition, the mounting of therapeutic agents onto these nanoparticles has resulted in significantly increased performance of the drugs when tested against particular disease states.

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

My research interests focus on the molecular mechanisms of blood pressure regulation and in particular the genetics of the renin-angiotensin-aldosterone system.

######Centre for Neuroregeneration, University of Edinburgh

In the developing vertebrate nervous system, oligodendrocytes and Schwann cells not only play a vital role in promoting neuron survival, but
they also produce the myelin sheath, which is essential for the normal function of the nervous system, a fact underscored by the debilitating consequences of demyelination in multiple sclerosis (CNS) and in peripheral neuropathies of the Charcot-Marie-Tooth (PNS) type. In one project we are building on our discovery of the Periaxin (Prx) gene in Schwann cells. Mice lacking a functional Prx gene ensheath and myelinate peripheral nerve axons in an apparently normal manner but the sheath later destabilizes and the mice develop a severe demyelinating neuropathy. In collaboration with colleagues in Paris we have identified a human disease called CMT-4F caused by similar mutations. In a second project, we have shown that two isoforms of neurofascin, one glial, the other neuronal, play distinct but vital roles in the assembly of the node of Ranvier. The role of these proteins during both normal development and during nerve repair is the subject of current work.

######School of Engineering, University of Edinburgh

My research specialisation include model-based Bayesian signal processing, speech and audio signal processing in adverse acoustic environments, including blind dereverberation and multi-target acoustic source localisation and tracking, single channel signal separation, distant speech recognition, audio-visual fusion, medical imaging, blind image deconvolution, and general statistical signal and image processing.

Prof Simon Herrington

######Institute of Genetics and Molecular Medicine, University of Edinburgh

My main research focus is the pathogenesis of anogenital epithelial neoplasia and how improved understanding of the mechanisms involved can be used to improve disease diagnosis. In addition to investigating the role of human papillomavirus infection in epithelial neoplasia, particularly of the female genital tract, the non-HPV-dependent pathway by which vulvar intraepithelial neoplasia (VIN) can develop is also of interest. This involves the investigation of ‘differentiated type’ VIN, which is the precursor of keratinising squamous cell carcinomas and occurs particularly in patients with lichen sclerosus. This entity provides the opportunity to investigate the development of invasive carcinoma in the context of retained epithelial differentiation. I am also interested in the use of optical imaging for the early detection of epithelial neoplasia.
In addition, in collaboration with the University of St Andrew, we are developing spectroscopic approaches for the early detection of epithelial neoplasia utilizing cross disciplinary experimental and theoretical techniques. This work aims to develop technology that can discriminate between normal and neoplastic cells and tissues with the aim of applying these novel methods to clinical samples.

Prof Lee Smith

######MRC Centre for Reproductive Health, University of Edinburgh

The adult testis is essentially a factory, which produces two key products, steroid hormones, notably testosterone and mature sperm from spermatogonial stem cells. Our current work is focused upon dissecting the mechanisms underlying these, using novel transgenic mouse models coupled to a wide variety of cutting edge molecular genetic and endocrinological techniques. In addition to this, we have extended our studies to investigate mouse models with targeted deletion of AR in the other body systems, including the cardiovascular system, adipose tissue and prostate. Together, these investigations highlight a body-wide and lifelong role for androgen-signalling in supporting lifelong health and wellbeing in men. Our future focus is now on understanding how androgen production is controlled within the testis and how this influences not only male fertility, but also other important clinical problems such as cardiovascular disease, diabetes, and age-related conditions.

Prof Ted Hupp

######Institute for Genetics and Molecular Medicine, University of Edinburgh

Cancer progression in is driven in part by the mutation of genes that mediate immortality, angiogenesis, metastasis, changes in energy metabolism, and evasion of the immune system. P53 mutation is one of the most common genetic changes in cancer development that leads to a re-wiring and selective survival advantage to the developing cancer cell. This genetic re-wiring involves changes in the transciptome, the proteome, and the phenotype of the cell within a specific microenvironmental niche in vivo. The lab is using biophysical, biochemical, and proteomic approaches to develop novel molecular insights into clinically relevant cancer progression pathways.

Prof Hilary Critchley

######MRC Centre for Reproductive Health, University of Edinburgh

Our research specifically examines local mechanisms within the womb-lining (endometrium) involved in menstruation, implantation and early pregnancy loss. Both menstruation and implantation display features common to inflammatory events. We study the cascade of events that occur in cells of the endometrium that are triggered by withdrawal of the hormone, progesterone which occurs at the end of each monthly cycle prior to a period. We are interested in the complex dialogue between circulating steroid hormones and the many different cell types, including immune cells that constitute the endometrium. We also study factors that switch on production of molecules involved in blood vessel growth and repair in the endometrium; both necessary events to prepare for the next menstrual cycle. If we can understand how the womb heals itself without scarring as women go through their menstrual cycles we hope we will contribute valuable information relevant to inflammation and scarring throughout the body. If these events are disturbed then abnormal menstrual bleeding may be the result. We hope that information about the molecular and cellular pathways involved in menstruation will help identify new targets for treatment, especially if these treatments could be delivered directly to the uterus.

######Institute of Genetics and Molecular Medicine, University of Edinburgh

My main research focus is the pathogenesis of anogenital epithelial neoplasia and how improved understanding of the mechanisms involved can be used to improve disease diagnosis. In addition to investigating the role of human papillomavirus infection in epithelial neoplasia, particularly of the female genital tract, the non-HPV-dependent pathway by which vulvar intraepithelial neoplasia (VIN) can develop is also of interest. This involves the investigation of ‘differentiated type’ VIN, which is the precursor of keratinising squamous cell carcinomas and occurs particularly in patients with lichen sclerosus. This entity provides the opportunity to investigate the development of invasive carcinoma in the context of retained epithelial differentiation. I am also interested in the use of optical imaging for the early detection of epithelial neoplasia.
In addition, in collaboration with the University of St Andrew, we are developing spectroscopic approaches for the early detection of epithelial neoplasia utilizing cross disciplinary experimental and theoretical techniques. This work aims to develop technology that can discriminate between normal and neoplastic cells and tissues with the aim of applying these novel methods to clinical samples.

######MRC Centre for Reproductive Health, University of Edinburgh

The adult testis is essentially a factory, which produces two key products, steroid hormones, notably testosterone and mature sperm from spermatogonial stem cells. Our current work is focused upon dissecting the mechanisms underlying these, using novel transgenic mouse models coupled to a wide variety of cutting edge molecular genetic and endocrinological techniques. In addition to this, we have extended our studies to investigate mouse models with targeted deletion of AR in the other body systems, including the cardiovascular system, adipose tissue and prostate. Together, these investigations highlight a body-wide and lifelong role for androgen-signalling in supporting lifelong health and wellbeing in men. Our future focus is now on understanding how androgen production is controlled within the testis and how this influences not only male fertility, but also other important clinical problems such as cardiovascular disease, diabetes, and age-related conditions.

######Institute for Genetics and Molecular Medicine, University of Edinburgh

Cancer progression in is driven in part by the mutation of genes that mediate immortality, angiogenesis, metastasis, changes in energy metabolism, and evasion of the immune system. P53 mutation is one of the most common genetic changes in cancer development that leads to a re-wiring and selective survival advantage to the developing cancer cell. This genetic re-wiring involves changes in the transciptome, the proteome, and the phenotype of the cell within a specific microenvironmental niche in vivo. The lab is using biophysical, biochemical, and proteomic approaches to develop novel molecular insights into clinically relevant cancer progression pathways.

######MRC Centre for Reproductive Health, University of Edinburgh

Our research specifically examines local mechanisms within the womb-lining (endometrium) involved in menstruation, implantation and early pregnancy loss. Both menstruation and implantation display features common to inflammatory events. We study the cascade of events that occur in cells of the endometrium that are triggered by withdrawal of the hormone, progesterone which occurs at the end of each monthly cycle prior to a period. We are interested in the complex dialogue between circulating steroid hormones and the many different cell types, including immune cells that constitute the endometrium. We also study factors that switch on production of molecules involved in blood vessel growth and repair in the endometrium; both necessary events to prepare for the next menstrual cycle. If we can understand how the womb heals itself without scarring as women go through their menstrual cycles we hope we will contribute valuable information relevant to inflammation and scarring throughout the body. If these events are disturbed then abnormal menstrual bleeding may be the result. We hope that information about the molecular and cellular pathways involved in menstruation will help identify new targets for treatment, especially if these treatments could be delivered directly to the uterus.

Dr Marc Dweck

######University/British Heart Foundation Centre for Cardiovascular Science

I am interested in the use of modern imaging techniques to investigate the pathophysiology of aortic stenosis. Primarily combined positron emission tomography and computed tomography (PET/CT) to study inflammation and calcification within the valve and cardiovascular magnetic resonance (CMR) to study fibrosis both within the valve and the hypertrophied myocardium. These studies form the basis of my British Heart Foundation Clinical PhD training fellowship and my recent Intermediate Clinical Research Fellowship. More recently I have become interested in the application of PET/CT to the detection of high-risk atherosclerotic plaque that has led to major funding investigating whether 18F-Fluoride can improve the prediction of myocardial infarction.

Prof Mark Bradley

######School of Chemistry, University of Edinburgh

My group’s research is highly diverse including microarrays (cells, small molecules, and polymers); cellular delivery (DNA, proteins, peptides); high-throughput chemistry and optical imaging.

However three research themes dominate our work at this time.

• The development of smart fluorescent reporters for clinical optical imaging - including probes for imaging cancer in vivo in real-time.
• The development and exploitation of polymer microarray technology for the identification and application of polymers for controlling and modulating cells - including the isolation of cancer stem cells
• In vivo catalytic chemistry - with a focus on Pd(0) in situ synthesis of cancer drugs.

Dr Marc Vendrell

######Centre for Inflammation Research, University of Edinburgh

The aim of our research is to develop fluorescent chemical probes as optical imaging tools to interrogate in situ and in real time, key events associated to cancer and inflammation. These probes will be eventually applied in man as new diagnostics tools with high specificity and molecular resolution. Our probes target relevant biomarkers in cancer and inflammation, and are generated through a multidisciplinary approach that involves organic chemistry, cell biology, imaging and medicine. Activatable fluorescent probes are advantageous in that their fluorescent signal is triggered by a target molecule (e.g. protein, enzyme, metabolite) or a specific environment (e.g. subcellular organelle); hence they emit fluorescence only after they interaction with the specific target. This strategy leads to optimum signal-to-noise ratios with increased sensitivity over other optical imaging approaches and enables their use in small concentrations reducing any potential adverse effects and facilitating the translation to clinical applications.

Prof Val Brunton

######Institute for Genetics and Molecular Medicine, University of Edinburgh

Tumour cells metastasise via a series of discrete biological processes that allow cells to disseminate from the primary tumour, move and colonise distant sites within the body. Our research focuses on understanding the molecular mechanisms whereby tumour cells can metastasise. We are using mouse models of metastatic cancer carrying fluorescent reporters that allow us to follow the metastatic process in real time using whole body imaging, while high resolution intravital microscopy allows us to follow the behaviour of single cells in the tumour micro-environment. This provides a unique way to study these processes and allows us to monitor drug efficacy and mechanism of action of new molecularly targeted agents that are currently in clinical development. We hope that this approach will lead to the development of more effective treatment strategies.

######University/British Heart Foundation Centre for Cardiovascular Science

I am interested in the use of modern imaging techniques to investigate the pathophysiology of aortic stenosis. Primarily combined positron emission tomography and computed tomography (PET/CT) to study inflammation and calcification within the valve and cardiovascular magnetic resonance (CMR) to study fibrosis both within the valve and the hypertrophied myocardium. These studies form the basis of my British Heart Foundation Clinical PhD training fellowship and my recent Intermediate Clinical Research Fellowship. More recently I have become interested in the application of PET/CT to the detection of high-risk atherosclerotic plaque that has led to major funding investigating whether 18F-Fluoride can improve the prediction of myocardial infarction.

######School of Chemistry, University of Edinburgh

My group’s research is highly diverse including microarrays (cells, small molecules, and polymers); cellular delivery (DNA, proteins, peptides); high-throughput chemistry and optical imaging.

However three research themes dominate our work at this time.

• The development of smart fluorescent reporters for clinical optical imaging - including probes for imaging cancer in vivo in real-time.
• The development and exploitation of polymer microarray technology for the identification and application of polymers for controlling and modulating cells - including the isolation of cancer stem cells
• In vivo catalytic chemistry - with a focus on Pd(0) in situ synthesis of cancer drugs.

######Centre for Inflammation Research, University of Edinburgh

The aim of our research is to develop fluorescent chemical probes as optical imaging tools to interrogate in situ and in real time, key events associated to cancer and inflammation. These probes will be eventually applied in man as new diagnostics tools with high specificity and molecular resolution. Our probes target relevant biomarkers in cancer and inflammation, and are generated through a multidisciplinary approach that involves organic chemistry, cell biology, imaging and medicine. Activatable fluorescent probes are advantageous in that their fluorescent signal is triggered by a target molecule (e.g. protein, enzyme, metabolite) or a specific environment (e.g. subcellular organelle); hence they emit fluorescence only after they interaction with the specific target. This strategy leads to optimum signal-to-noise ratios with increased sensitivity over other optical imaging approaches and enables their use in small concentrations reducing any potential adverse effects and facilitating the translation to clinical applications.

######Institute for Genetics and Molecular Medicine, University of Edinburgh

Tumour cells metastasise via a series of discrete biological processes that allow cells to disseminate from the primary tumour, move and colonise distant sites within the body. Our research focuses on understanding the molecular mechanisms whereby tumour cells can metastasise. We are using mouse models of metastatic cancer carrying fluorescent reporters that allow us to follow the metastatic process in real time using whole body imaging, while high resolution intravital microscopy allows us to follow the behaviour of single cells in the tumour micro-environment. This provides a unique way to study these processes and allows us to monitor drug efficacy and mechanism of action of new molecularly targeted agents that are currently in clinical development. We hope that this approach will lead to the development of more effective treatment strategies.

Prof Gail McConnell

######Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde

My research background is in photonics and the development of optical instrumentation. My present research applies this expertise to develop and apply innovative novel optical systems to address fundamental challenges faced in biological imaging. As the life sciences communities continue to embrace optical imaging, the growing range of applications places greater demands on the optical technology required. Robust and simple to use systems are sought to improve the efficiency and ease of existing imaging techniques. Nonlinear optics has demonstrated great potential in creating useful solutions for advanced optical imaging, exploiting higher order effects not only to improve existing imaging methods but also to assist with the creation of new imaging techniques. Current projects involve innovations in nonlinear optics to create new enabling technologies. These include custom-designed laser systems for coherent anti-Stokes Raman scattering microscopy, the creation of 'open source' laser scanning microscopy platforms, the application of optical methods to control the function and behaviour of biological organisms and the development of diagnostic tools and measurement techniques applied in optical imaging.

Dr Javier Escudero

######School of Engineering, University of Edinburgh

I am a signal processing engineer who analyses biomedical data. My main aim is to reveal the subtle changes that major diseases (e.g., Alzheimer's and epilepsy) cause in the brain activity and how this changes in different conditions and mental states. In collaboration with researchers at Edinburgh, across the UK and overseas, I am currently working in the processing and analysis of biomedical signals, particularly human brain activity. By applying advanced mathematics, I aim at increasing our understanding of how several brain conditions progress. I have expertise in noise reduction and feature extraction for diverse biomedical recordings. Of particular interest is the evaluation of brain functional connectivity in both neurodevelopmental and neurodegenerative diseases to understand how they affect the way in which different brain regions interact with each other. I am also interested in the application of pattern recognition techniques to highly-dimensional clinical datasets to support decision making and in the development of non-invasive methods for rehabilitation purposes, being either the dexterous controls prostheses for amputees or brain-computer interfaces.

Dr Pierre Bagnaninchi

######School of Engineering, University of Edinburgh

Our main research interest is the development of non-destructive quantitative monitoring technologies for regenerative medicine to monitor cell distribution, viability and identity in 2D and 3D cell therapies delivery vehicles (film, scaffold, gels, matrices). These technologies will help us to establish a quality-control of cell-based products before they are used in the clinic. They also address the need for real-time monitoring of in vitro disease models. Our current projects are Optical coherence tomography for tissue engineering and regenerative medicine; and non-invasive biosensors and quantitative methods in medicine and biology

Dr Olaf Rolinsky

######Department of Physics, University of Strathclyde

My group’s main research goal is developing new fluorescence sensors based on nanometre distance-dependent molecular interactions. We specialise in fluorescence lifetime based sensing, particularly fluorescence resonance energy transfer (FRET) sensors for structural, metal ion and metabolite detection. We developed the method to determine the donor-acceptor distribution functions from FRET experiment data. We are involved in structural studies of phospholipid assemblies, sol-gels and porous polymers. Our biomedical research interests include: analyte-induced conformational changes of proteins monitored by fluorescence and specially designed FRET systems.

######Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde

My research background is in photonics and the development of optical instrumentation. My present research applies this expertise to develop and apply innovative novel optical systems to address fundamental challenges faced in biological imaging. As the life sciences communities continue to embrace optical imaging, the growing range of applications places greater demands on the optical technology required. Robust and simple to use systems are sought to improve the efficiency and ease of existing imaging techniques. Nonlinear optics has demonstrated great potential in creating useful solutions for advanced optical imaging, exploiting higher order effects not only to improve existing imaging methods but also to assist with the creation of new imaging techniques. Current projects involve innovations in nonlinear optics to create new enabling technologies. These include custom-designed laser systems for coherent anti-Stokes Raman scattering microscopy, the creation of 'open source' laser scanning microscopy platforms, the application of optical methods to control the function and behaviour of biological organisms and the development of diagnostic tools and measurement techniques applied in optical imaging.

######School of Engineering, University of Edinburgh

I am a signal processing engineer who analyses biomedical data. My main aim is to reveal the subtle changes that major diseases (e.g., Alzheimer's and epilepsy) cause in the brain activity and how this changes in different conditions and mental states. In collaboration with researchers at Edinburgh, across the UK and overseas, I am currently working in the processing and analysis of biomedical signals, particularly human brain activity. By applying advanced mathematics, I aim at increasing our understanding of how several brain conditions progress. I have expertise in noise reduction and feature extraction for diverse biomedical recordings. Of particular interest is the evaluation of brain functional connectivity in both neurodevelopmental and neurodegenerative diseases to understand how they affect the way in which different brain regions interact with each other. I am also interested in the application of pattern recognition techniques to highly-dimensional clinical datasets to support decision making and in the development of non-invasive methods for rehabilitation purposes, being either the dexterous controls prostheses for amputees or brain-computer interfaces.

######School of Engineering, University of Edinburgh

Our main research interest is the development of non-destructive quantitative monitoring technologies for regenerative medicine to monitor cell distribution, viability and identity in 2D and 3D cell therapies delivery vehicles (film, scaffold, gels, matrices). These technologies will help us to establish a quality-control of cell-based products before they are used in the clinic. They also address the need for real-time monitoring of in vitro disease models. Our current projects are Optical coherence tomography for tissue engineering and regenerative medicine; and non-invasive biosensors and quantitative methods in medicine and biology

######Department of Physics, University of Strathclyde

My group’s main research goal is developing new fluorescence sensors based on nanometre distance-dependent molecular interactions. We specialise in fluorescence lifetime based sensing, particularly fluorescence resonance energy transfer (FRET) sensors for structural, metal ion and metabolite detection. We developed the method to determine the donor-acceptor distribution functions from FRET experiment data. We are involved in structural studies of phospholipid assemblies, sol-gels and porous polymers. Our biomedical research interests include: analyte-induced conformational changes of proteins monitored by fluorescence and specially designed FRET systems.

Prof Seth Grant

######Centre for Neuroregeneration, University of Edinburgh

Our research has focussed on the study of genes and proteins that control the synapses between nerve cells. Multiprotein machines comprising many different protein components are responsible for basic innate and learned behaviours and dysfunction in many brain diseases. Recent work shows that these mechanisms are conserved between mice and humans opening new avenues for diagnosis and therapeutic discoveries.
These protein complexes are microscopic molecular machines inside synapses - the junctions between nerve cells. Molecular proteomic studies show there are more than 1000 synapse proteins working together to process information in the brain.
Multiprotein complexes are involved with dozens of brain diseases, control multiple types of behaviours and are involved with the responses to drug treatments of mental disorders. Evolutionary studies show ancient forms of the complexes evolved over a billion years in single cell animals and may represent the origin of the brain.
Our long term goal is to understand the molecular basis of the extraordinarily complex brain of humans, how this complexity evolved, what it confers on behaviour and why brain evolution made us susceptible to mental illness.

Dr Kev Dhaliwal

######MRC Centre for Inflammation Research, University of Edinburgh

Our group is multidisciplinary and has two broad themes 1) Focussed on discovering new methodologies that will permit the accurate and spatial characterisation of inflammation, infection and fibrosis in the distal human lung. We work alongside chemistry, physics, engineering, image analysis and informatics to develop optical molecular imaging strategies. 2) Understanding the pulmonary response to acute infection and inflammation with a particular interest in monocyte/macrophage biology and neutrophil recruitment.
Current research projects in the lab include developing novel point-of-care diagnostics for bacterial detection in the distal lung, drug-stratification tools in acute lung injury and mechanisms to monitor the fibroproliferative pathway. We are also interested in understanding and defining the contribution of damage-associated molecular pattern molecules in pulmonary infection and organ injury

Prof Margaret Frame

######Institute of Genetics and Molecular Medicine, University of Edinburgh

My long-held research interests are cancer invasion and metastasis, and the role of tyrosine kinases in controlling tumour cell spread. I have had several CR-UK funded programs of research to work on understanding cancer invasion and metastasis, the key hallmarks of malignancy, and was recently awarded an ERC Advanced Investigator grant to build a novel cancer discovery platform. Our major goal is to work with clinicians treating cancers of unmet need, to determine whether, and if so how, targeting the invasive and metastatic processes may be therapeutically beneficial, and may be monitored in the preclinical and clinical settings by novel imaging techniques.

Dr Liz Patton

######Institute of Genetics and Molecular Medicine, University of Edinburgh

Melanoma accounts for 80% of the deaths from skin cancer, and incidence continues to rise rapidly. Aggressive and resistant to chemotherapies, individuals with metastatic melanoma often have a life expectancy of less than one year. Our research is focused on understanding how melanocytes – the pigment cells that become melanoma – develop, divide, migrate and maintain homeostasis within their microenvironment, as well as the genetic and cellular events that cause melanocytes to form moles and their progression to invasive cancer. To do this, we use the zebrafish system, which allows both the visualization of developing and migrating melanocytes, as well as their aberrant progression to melanoma. The zebrafish is a powerful model system to study developmental biology, chemical biology and disease models. Due to the similar genetic, molecular and cancer pathology between humans and fish, our melanoma progression model can be viewed as an important starting point for identifying novel genes, environmental conditions, and therapeutic compounds that affect melanoma progression.

######Centre for Neuroregeneration, University of Edinburgh

Our research has focussed on the study of genes and proteins that control the synapses between nerve cells. Multiprotein machines comprising many different protein components are responsible for basic innate and learned behaviours and dysfunction in many brain diseases. Recent work shows that these mechanisms are conserved between mice and humans opening new avenues for diagnosis and therapeutic discoveries.
These protein complexes are microscopic molecular machines inside synapses - the junctions between nerve cells. Molecular proteomic studies show there are more than 1000 synapse proteins working together to process information in the brain.
Multiprotein complexes are involved with dozens of brain diseases, control multiple types of behaviours and are involved with the responses to drug treatments of mental disorders. Evolutionary studies show ancient forms of the complexes evolved over a billion years in single cell animals and may represent the origin of the brain.
Our long term goal is to understand the molecular basis of the extraordinarily complex brain of humans, how this complexity evolved, what it confers on behaviour and why brain evolution made us susceptible to mental illness.

######MRC Centre for Inflammation Research, University of Edinburgh

Our group is multidisciplinary and has two broad themes 1) Focussed on discovering new methodologies that will permit the accurate and spatial characterisation of inflammation, infection and fibrosis in the distal human lung. We work alongside chemistry, physics, engineering, image analysis and informatics to develop optical molecular imaging strategies. 2) Understanding the pulmonary response to acute infection and inflammation with a particular interest in monocyte/macrophage biology and neutrophil recruitment.
Current research projects in the lab include developing novel point-of-care diagnostics for bacterial detection in the distal lung, drug-stratification tools in acute lung injury and mechanisms to monitor the fibroproliferative pathway. We are also interested in understanding and defining the contribution of damage-associated molecular pattern molecules in pulmonary infection and organ injury

######Institute of Genetics and Molecular Medicine, University of Edinburgh

My long-held research interests are cancer invasion and metastasis, and the role of tyrosine kinases in controlling tumour cell spread. I have had several CR-UK funded programs of research to work on understanding cancer invasion and metastasis, the key hallmarks of malignancy, and was recently awarded an ERC Advanced Investigator grant to build a novel cancer discovery platform. Our major goal is to work with clinicians treating cancers of unmet need, to determine whether, and if so how, targeting the invasive and metastatic processes may be therapeutically beneficial, and may be monitored in the preclinical and clinical settings by novel imaging techniques.

######Institute of Genetics and Molecular Medicine, University of Edinburgh

Melanoma accounts for 80% of the deaths from skin cancer, and incidence continues to rise rapidly. Aggressive and resistant to chemotherapies, individuals with metastatic melanoma often have a life expectancy of less than one year. Our research is focused on understanding how melanocytes – the pigment cells that become melanoma – develop, divide, migrate and maintain homeostasis within their microenvironment, as well as the genetic and cellular events that cause melanocytes to form moles and their progression to invasive cancer. To do this, we use the zebrafish system, which allows both the visualization of developing and migrating melanocytes, as well as their aberrant progression to melanoma. The zebrafish is a powerful model system to study developmental biology, chemical biology and disease models. Due to the similar genetic, molecular and cancer pathology between humans and fish, our melanoma progression model can be viewed as an important starting point for identifying novel genes, environmental conditions, and therapeutic compounds that affect melanoma progression.

Dr Glenn Burley

######Department of Pure and Applied Chemistry, University of Strathclyde

Our research is focused on the chemistry and biology of nucleotides, nucleic acids and nucleic acid binding molecules. Some of our research programmes are: 1. Chemical Biology of alternative RNA splicing. This work is aimed at unravelling fundamental issues associated with alternative splice site selection using small molecule and large molecule (oligonucleotides and protein hybrids) probes and how these processes are affected in disease states such as Spinal Muscular Atrophy and cancer. 2. DNA-based construction of molecular devices. We are currently developing new chemical biological approaches for the construction of optoelectronic devices. This is being achieved by synthesizing DNA binding molecules which effectively read the genetic code of DNA in order to locate a particular metal or a magnet to a particular destination along the DNA template. We are now applying this technology to investigate the utility of these constructs as light-harvesting devices and plasmonic waveguides for molecular electronics and medical diagnostic applications.

Dr Vasileios Koutsos

######School of Engineering, University of Edinburgh

We are interested in the behaviour of soft materials and complex fluids at surfaces & interfaces. Complex fluids consisting of two or more components, such as nanocolloid or polymer suspensions, polymer blends, block copolymers, exhibit unusual physical properties due to the geometric constraints imposed by the coexistence of the different phases. When confined on surfaces, there is an additional geometric constraint which induces further changes in their behaviour. Polymers and nanocolloids can self-assemble into a variety of nanostructures and nanopatterns at interfaces offering alternative ways of facile and inexpensive nanofabrication routes which have great potential for many applications ranging from micro/nanoelectronics to biomedical implants.

Prof Moira Whyte

######Centre for Inflammation Research, University of Edinburgh

My research interests have focussed on molecular mechanisms of innate immune cell apoptosis in the context both of chronic inflammatory lung disease and of host defence against bacterial infection. These are areas of major therapeutic challenge with no effective therapies for persistent neutrophilic inflammation and with strategies to manipulate host immune responses to pathogens having exciting potential for treatment of antibiotic-resistance infection.

Prof Margarete Heck

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

The research in our laboratory uses Drosophila melanogaster in order to exploit classical and molecular genetics in an organism amenable to developmental and cytological analysis. We have been studying a novel metalloprotease that we identified as a result of a unique mitotic phenotype affecting chromosome structure, spindle assembly, and the dynamics of nuclear envelope proteins. We propose that this protease is essential for the coordination of mitotic structural rearrangements. This protease defines a novel family of proteases with homology to leishmanolysin, from Leishmania species. We originally postulated the unusual ring-like structures that this protein is found in to be invadopodia – and hence named the protein invadolysin. Current research is focused on identifying substrates and regulators of invadolysin in order to understand its mechanism of action, analysing model systems such as the fly and fish to study in vivo function, and examining the fate of the protein in cellular in vitro differentiation systems. Ultimately, we hope to understand the role of the protein in normal and human disease states in which migration and/or proliferation of cells play crucial roles.

######Department of Pure and Applied Chemistry, University of Strathclyde

Our research is focused on the chemistry and biology of nucleotides, nucleic acids and nucleic acid binding molecules. Some of our research programmes are: 1. Chemical Biology of alternative RNA splicing. This work is aimed at unravelling fundamental issues associated with alternative splice site selection using small molecule and large molecule (oligonucleotides and protein hybrids) probes and how these processes are affected in disease states such as Spinal Muscular Atrophy and cancer. 2. DNA-based construction of molecular devices. We are currently developing new chemical biological approaches for the construction of optoelectronic devices. This is being achieved by synthesizing DNA binding molecules which effectively read the genetic code of DNA in order to locate a particular metal or a magnet to a particular destination along the DNA template. We are now applying this technology to investigate the utility of these constructs as light-harvesting devices and plasmonic waveguides for molecular electronics and medical diagnostic applications.

######School of Engineering, University of Edinburgh

We are interested in the behaviour of soft materials and complex fluids at surfaces & interfaces. Complex fluids consisting of two or more components, such as nanocolloid or polymer suspensions, polymer blends, block copolymers, exhibit unusual physical properties due to the geometric constraints imposed by the coexistence of the different phases. When confined on surfaces, there is an additional geometric constraint which induces further changes in their behaviour. Polymers and nanocolloids can self-assemble into a variety of nanostructures and nanopatterns at interfaces offering alternative ways of facile and inexpensive nanofabrication routes which have great potential for many applications ranging from micro/nanoelectronics to biomedical implants.

######Centre for Inflammation Research, University of Edinburgh

My research interests have focussed on molecular mechanisms of innate immune cell apoptosis in the context both of chronic inflammatory lung disease and of host defence against bacterial infection. These are areas of major therapeutic challenge with no effective therapies for persistent neutrophilic inflammation and with strategies to manipulate host immune responses to pathogens having exciting potential for treatment of antibiotic-resistance infection.

######University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh

The research in our laboratory uses Drosophila melanogaster in order to exploit classical and molecular genetics in an organism amenable to developmental and cytological analysis. We have been studying a novel metalloprotease that we identified as a result of a unique mitotic phenotype affecting chromosome structure, spindle assembly, and the dynamics of nuclear envelope proteins. We propose that this protease is essential for the coordination of mitotic structural rearrangements. This protease defines a novel family of proteases with homology to leishmanolysin, from Leishmania species. We originally postulated the unusual ring-like structures that this protein is found in to be invadopodia – and hence named the protein invadolysin. Current research is focused on identifying substrates and regulators of invadolysin in order to understand its mechanism of action, analysing model systems such as the fly and fish to study in vivo function, and examining the fate of the protein in cellular in vitro differentiation systems. Ultimately, we hope to understand the role of the protein in normal and human disease states in which migration and/or proliferation of cells play crucial roles.

Prof Stuart Forbes

######MRC Centre for Regenerative Medicine, University of Edinburgh

Liver disease is the 5th commonest cause of death in the UK and the deaths from cirrhosis are rapidly rising. Currently the only curative option for end-stage liver disease is liver transplantation. Donor organ availability cannot even meet current demand and many patients die whilst waiting for a suitable organ. Alternative therapeutic strategies are urgently required for the treatment of advanced liver disease. Our program of research concentrates on understanding how the Hepatic Progenitor Cells regenerate the liver in chronic disease and how this process becomes deranged in the development of liver cancer. By understanding what controls this process we aim to be able to promote healthy liver regeneration and reduce the formation of liver cirrhosis and cancer.
We are also developing pre-clinical and clinical tools to stimulate liver regeneration and reduce scarring using cell therapy. In particular we have found that bone marrow derived macrophages can promote liver regeneration and reduce scarring and this is being developed as a clinical therapy.

######MRC Centre for Regenerative Medicine, University of Edinburgh

Liver disease is the 5th commonest cause of death in the UK and the deaths from cirrhosis are rapidly rising. Currently the only curative option for end-stage liver disease is liver transplantation. Donor organ availability cannot even meet current demand and many patients die whilst waiting for a suitable organ. Alternative therapeutic strategies are urgently required for the treatment of advanced liver disease. Our program of research concentrates on understanding how the Hepatic Progenitor Cells regenerate the liver in chronic disease and how this process becomes deranged in the development of liver cancer. By understanding what controls this process we aim to be able to promote healthy liver regeneration and reduce the formation of liver cirrhosis and cancer.
We are also developing pre-clinical and clinical tools to stimulate liver regeneration and reduce scarring using cell therapy. In particular we have found that bone marrow derived macrophages can promote liver regeneration and reduce scarring and this is being developed as a clinical therapy.

OPTIMA2014 Cohort

Affectionately known as the "guinea pigs", these trail-blazing students are very much part of the team building OPTIMA. Their experiences and feedback are helping us shape our CDT into a responsive, student-centred programme.

Each project represents interdisciplinary research at its best: from a physicist developing gold nanorods as biosensors in melanoma diagnosis, to a medicinal chemist developing imaging techniques for extracellular vesicles in a lymphoma model. This cohort is the epitome of the OPTIMA vision - new eyes on old problems will create innovative clinical solutions and opportunities.

Ms Alisia Sim

I’ve joined the Optima CDT programme in September 2014 working on the detection of microcalcification in vulnerable atherosclerotic plaques using fluorescent probes under the supervision of Alison Hulme, Fabio Nudelman and Marc Dweck.
PET imaging using the bone tracer Na18F is currently employed to locate atherosclerotic plaques in a non-invasive manner. These plaques are often at risk of rupture and therefore can lead to myocardial infarction. A disadvantage of PET imaging is the limited spatial resolution, 4-5 mm, which limits the mechanistic information that can be obtained using this technique. New technology, such as optical coherence tomography (OCT) and optical imaging techniques, can allow for much higher spatial resolution than PET. The combination of the currently used PET/OCT technique together with imaging techniques could allow us to obtain anatomical information on fibrous cap thickness, lipid core size and percentage lipid content which have not been attained before.
I have always been fascinated by chemistry and especially innovation. It never ceases to excite me how basic discoveries can become drivers of societal change, not just medicines, diagnostics, or ingredients of household goods. What attracted me to his CDT was the possibility of having access to the rapidly developing field of medical imaging and that my research could have potential medical and diagnostic applications that could be converted into a commercial product or service. Understanding how to translate science into a commercial reality and how to bring it to the market is the reason I applied for this PhD.

Mr Thane Campbell

Neutrophil elastase is the signature enzyme of our immune system’s first line of defence. Neutrophils are a ferocious white blood cell designed to rapidly disassemble agents of disease before the first symptoms. Unfortunately chronic immune states develop with excessive neutrophil activity, precipitating staggering collateral damage in the most common and incurable diseases. My research investigates the consequences of neutrophil recruitment in human lung cancer, atherosclerosis and ulcerative colitis. I will optically image neutrophil elastase presence and activity to both identify neutrophils and describe their biological effect using “SmartProbes”. SmartProbes are engineered to use a key biological step to activate coloured fluorescent light. Extracting the critical information with this binary signal simplifies complex biological processes like inflammation, relaying this information non-invasively, without ionising radiation and cheaply. Working with GlaxoSmithKline, I will iteratively develop and test these SmartProbes for their applications in drug discovery, patient stratification and real-time monitoring.
I chose the OPTIMA CDT because I value ambition. Optical imaging is an expansive and dynamic field that now describes living systems beyond the diffraction limit of light. The OPTIMA CDT places students at the cutting-edge of scientific endeavour and equips us to commercialize innovation there for the benefit of research, patients and the economy.

Ms Catherine Lynch

It has been known for some time that a number of cell types are capable of releasing membrane-enclosed vesicles into the extracellular environment in response to various stimuli. However the full scope of the function of extracellular vesicles is only beginning to be revealed. It has been shown that extracellular vesicles can cargo protein or genetic cargo, and may be tools of cell-to-cell communication. Production of extracellular vesicles can be upregulated in disease states such as cancer; so examining the burden and cargo of extracellular vesicles in patients could be beneficial for diagnosis, prognosis, or treatment indication.
The aim of my project is to examine the release of extracellular vesicles in a model of non-Hodgkin’s lymphoma. Identifying plasma membrane surface proteins which are upregulated in cancer gives indications of possible proteins retained on the membrane enclosing the extracellular vesicle, and these can be used as targets for imaging using SERS. The ability to detect extracellular vesicles in the blood of patients without the need for an isolation step could potentially be beneficial for clinical use.
Having studied medicinal chemistry, I have always been interested in the practical health applications of scientific research, so Optima seemed like the right option for me. The business aspect of the course was something I’d never considered before, but it’s interesting to learn more about the processes behind commercialisation of scientific discoveries.

Mr Sam Stanfield

Doctors who want to gain an understanding about the physiological conditions within a patients lungs currently have two main options, an x-ray or a biopsy; the former provides little detail in information whilst the latter is time consuming and difficult.
I am working as part of the Proteus research group, who aim to develop an optical fibre-based healthcare technology to perform real-time imaging and sensing deep within the patient’s lungs. My research focusses on the sensing aspect of the fibre by developing Surface-Enhanced Raman Spectroscopy (SERS) based nanosensors, which whilst attached to the tip of the fibre allow users to perform quantitative analyses of molecules and conditions present in blood and tissue, particularly redox potential and glucose concentration.
Nanoparticle surfaces can be functionalised with a variety of sensing molecules dependant upon requirement. Glucose sensors are designed with an affinity and specificity for glucose molecules over other interfering molecules. Peaks specific to the Raman spectrum of glucose can then be detected and its concentration calculated. For the measurement of redox potential, sensors are designed with a structure that reliably changes upon oxidation or reduction. This causes changes in the sensors Raman spectrum, which can be identified and used to calculate the redox potential.
I chose the OPTIMA CDT because I wanted the chance to learn how hard-won gains in scientific knowledge can be transferred from the research lab bench in to innovative technologies able to benefit society.

I’ve joined the Optima CDT programme in September 2014 working on the detection of microcalcification in vulnerable atherosclerotic plaques using fluorescent probes under the supervision of Alison Hulme, Fabio Nudelman and Marc Dweck.
PET imaging using the bone tracer Na18F is currently employed to locate atherosclerotic plaques in a non-invasive manner. These plaques are often at risk of rupture and therefore can lead to myocardial infarction. A disadvantage of PET imaging is the limited spatial resolution, 4-5 mm, which limits the mechanistic information that can be obtained using this technique. New technology, such as optical coherence tomography (OCT) and optical imaging techniques, can allow for much higher spatial resolution than PET. The combination of the currently used PET/OCT technique together with imaging techniques could allow us to obtain anatomical information on fibrous cap thickness, lipid core size and percentage lipid content which have not been attained before.
I have always been fascinated by chemistry and especially innovation. It never ceases to excite me how basic discoveries can become drivers of societal change, not just medicines, diagnostics, or ingredients of household goods. What attracted me to his CDT was the possibility of having access to the rapidly developing field of medical imaging and that my research could have potential medical and diagnostic applications that could be converted into a commercial product or service. Understanding how to translate science into a commercial reality and how to bring it to the market is the reason I applied for this PhD.

Neutrophil elastase is the signature enzyme of our immune system’s first line of defence. Neutrophils are a ferocious white blood cell designed to rapidly disassemble agents of disease before the first symptoms. Unfortunately chronic immune states develop with excessive neutrophil activity, precipitating staggering collateral damage in the most common and incurable diseases. My research investigates the consequences of neutrophil recruitment in human lung cancer, atherosclerosis and ulcerative colitis. I will optically image neutrophil elastase presence and activity to both identify neutrophils and describe their biological effect using “SmartProbes”. SmartProbes are engineered to use a key biological step to activate coloured fluorescent light. Extracting the critical information with this binary signal simplifies complex biological processes like inflammation, relaying this information non-invasively, without ionising radiation and cheaply. Working with GlaxoSmithKline, I will iteratively develop and test these SmartProbes for their applications in drug discovery, patient stratification and real-time monitoring.
I chose the OPTIMA CDT because I value ambition. Optical imaging is an expansive and dynamic field that now describes living systems beyond the diffraction limit of light. The OPTIMA CDT places students at the cutting-edge of scientific endeavour and equips us to commercialize innovation there for the benefit of research, patients and the economy.

It has been known for some time that a number of cell types are capable of releasing membrane-enclosed vesicles into the extracellular environment in response to various stimuli. However the full scope of the function of extracellular vesicles is only beginning to be revealed. It has been shown that extracellular vesicles can cargo protein or genetic cargo, and may be tools of cell-to-cell communication. Production of extracellular vesicles can be upregulated in disease states such as cancer; so examining the burden and cargo of extracellular vesicles in patients could be beneficial for diagnosis, prognosis, or treatment indication.
The aim of my project is to examine the release of extracellular vesicles in a model of non-Hodgkin’s lymphoma. Identifying plasma membrane surface proteins which are upregulated in cancer gives indications of possible proteins retained on the membrane enclosing the extracellular vesicle, and these can be used as targets for imaging using SERS. The ability to detect extracellular vesicles in the blood of patients without the need for an isolation step could potentially be beneficial for clinical use.
Having studied medicinal chemistry, I have always been interested in the practical health applications of scientific research, so Optima seemed like the right option for me. The business aspect of the course was something I’d never considered before, but it’s interesting to learn more about the processes behind commercialisation of scientific discoveries.

Doctors who want to gain an understanding about the physiological conditions within a patients lungs currently have two main options, an x-ray or a biopsy; the former provides little detail in information whilst the latter is time consuming and difficult.
I am working as part of the Proteus research group, who aim to develop an optical fibre-based healthcare technology to perform real-time imaging and sensing deep within the patient’s lungs. My research focusses on the sensing aspect of the fibre by developing Surface-Enhanced Raman Spectroscopy (SERS) based nanosensors, which whilst attached to the tip of the fibre allow users to perform quantitative analyses of molecules and conditions present in blood and tissue, particularly redox potential and glucose concentration.
Nanoparticle surfaces can be functionalised with a variety of sensing molecules dependant upon requirement. Glucose sensors are designed with an affinity and specificity for glucose molecules over other interfering molecules. Peaks specific to the Raman spectrum of glucose can then be detected and its concentration calculated. For the measurement of redox potential, sensors are designed with a structure that reliably changes upon oxidation or reduction. This causes changes in the sensors Raman spectrum, which can be identified and used to calculate the redox potential.
I chose the OPTIMA CDT because I wanted the chance to learn how hard-won gains in scientific knowledge can be transferred from the research lab bench in to innovative technologies able to benefit society.

Ms Evita Ning

The aim of my project is to use specifically designed chemical probes as optical imaging tools showing spectral changes in response to the interaction with defined target molecules. Use chromospheres as the Raman labels to functionalised nanoparticles that can give strong, unique Raman responses. In this project we will develop new Raman-active chromospheres as highly sensitive surface enhanced Raman probes. The specific reporters will be designed such that they will display Raman responses upon interaction with the target. I will explore chromospheres that undergo change in their chemical structure when reacting with the target binding, such that their resonance Raman responses can be tuned.

The advantage of using Raman rather than fluorescence as the optical imaging technique is the molecular specificity of the optical response, however more importantly in this case, is the combination of surface enhanced spectroscopy and SOR (spatially offset Raman, SESORS) which allows detection of Raman signals at depth. In this project the specific Raman probes will be designed to target bacteria within biofilms and also deep in tissue with a view to use SESORS for detection at depth through the skin. I will use model systems in the lab with live bacteria in tissue phantoms before moving to in vivo experiment.

CDT OPTIMA is the UK first jointed PhD degree between Edinburgh and Strathclyde University. Unlike the conventional PhD, this fascinating programme is not only training you to solving scientific problems, but also, to help to identify your entrepreneurial potential, and make the scientific invention into innovation, which will be beneficial to the society.

Mr Joe Willson

Neutrophils are our first line of defence against invading pathogens and mediate the onset of inflammation. Neutrophils are unusual cells in that they are terminally differentiated and have a constitutive apoptosis response following ageing in the body which aids their clearance from inflamed sites and subsequence resolution of inflammation. Apoptosis of neutrophils is delayed on exposure to hypoxic oxygen tensions comparable to those found at sites of inflammation. There are also a number of functional consequences involved in this neutrophil hypoxic survival phenotype, such as changes in cell movement and release of cytokines. The study of neutrophil apoptosis and clearance at low oxygen tensions is essential in probing diseases such as Chronic Obstructive Pulmonary Disease, where the degree of neutrophil persistence in the tissue corresponds with the severity of disease.

The aim of my project is to investigate the role of the neutrophil mitochondria in the context of neutrophil hypoxic survival and whether modulation of intracellular redox potential across different oxygen concentrations confers functional changes in the cell and the mitochondria, specifically. My project involves assessing mitochondrial function in normal and low oxygen through imaging the activity of a range of mitochondrial-specific functional dyes. I will also be using Surface Enhanced Raman Spectroscopy (SERS) to measure intracellular redox at different oxygen tensions.

The collaborative, multi-discipline aspect of the Optima CDT appealed to me greatly when applying and throughout the project has been invaluable in merging biological, chemical and physical aspects of the project into coherent, cross-discipline experiments.

Ms Holly Fleming

I joined the Centre for Doctoral Training in Optical Imaging in Sept 2014 aimed at developing fibre-based smartprobes and sensors for use in critically ill patients and am working the Bradley research team as well as being aligned to the EPSRC IRC Proteus. My research has two angles: (i). Creating nanoparticle-containing-polymers for use in SERS (surface-enhanced Raman spectroscopy) and (ii). Looking into developing optical labels for an enzyme involved in inflammation. This will involve synthesising and investigating small molecule inhibitors of human neutrophil elastase (HNE) and the use of SERS and fluorescence in its detection.
Having studied medicinal and biological chemistry throughout my undergraduate time, I have always enjoyed learning about the applications of chemistry, particularly in healthcare. I joined the CDT because it offered an excellent opportunity to be a part of applied research, and to learn about the stages involved in taking science from a lab scenario through to commercialisation.

Mr Alastair Davy

Nobel metal nanoparticles have received a large amount of attention in recent years, as their biomedical applications become realised. Of the nanoparticles available, the gold nanoparticle has great potential for biosensing and cancer treatment applications.
One of the advantages of gold nanorods is that their optical properties lie in the far visible and near infrared. Coupled with their ability to be excited via two photon illumination and low cytotoxicity means that the gold nanorod can be used for non-invasive bio sensing applications. Another advantage of the gold nanoparticle is that they can be developed into radiosensitizers, which are able to increase the dose of radiation in radiotherapy. This allows for lower and safer levels of radiation to be used when performing radiotherapy.
The aims of the project is to develop gold nanorods for cancer detection and treatment. In collaboration with the Cancer research centre at Edinburgh’s Institute of Genetic and Molecular Medicine I aim to use zebrafish embryos as an in vivo model for testing these gold nanoparticle biosensors. Then working with the National Physics Laboratory, I aim to develop the nanorods into radiosensitisers.
In today’s world the boundaries between scientific disciplines are merging and it fills me with great pride knowing that with the Optima program I am training to help cross these disciplines and bring about discoveries that could not have been achieved before.

The aim of my project is to use specifically designed chemical probes as optical imaging tools showing spectral changes in response to the interaction with defined target molecules. Use chromospheres as the Raman labels to functionalised nanoparticles that can give strong, unique Raman responses. In this project we will develop new Raman-active chromospheres as highly sensitive surface enhanced Raman probes. The specific reporters will be designed such that they will display Raman responses upon interaction with the target. I will explore chromospheres that undergo change in their chemical structure when reacting with the target binding, such that their resonance Raman responses can be tuned.

The advantage of using Raman rather than fluorescence as the optical imaging technique is the molecular specificity of the optical response, however more importantly in this case, is the combination of surface enhanced spectroscopy and SOR (spatially offset Raman, SESORS) which allows detection of Raman signals at depth. In this project the specific Raman probes will be designed to target bacteria within biofilms and also deep in tissue with a view to use SESORS for detection at depth through the skin. I will use model systems in the lab with live bacteria in tissue phantoms before moving to in vivo experiment.

CDT OPTIMA is the UK first jointed PhD degree between Edinburgh and Strathclyde University. Unlike the conventional PhD, this fascinating programme is not only training you to solving scientific problems, but also, to help to identify your entrepreneurial potential, and make the scientific invention into innovation, which will be beneficial to the society.

Neutrophils are our first line of defence against invading pathogens and mediate the onset of inflammation. Neutrophils are unusual cells in that they are terminally differentiated and have a constitutive apoptosis response following ageing in the body which aids their clearance from inflamed sites and subsequence resolution of inflammation. Apoptosis of neutrophils is delayed on exposure to hypoxic oxygen tensions comparable to those found at sites of inflammation. There are also a number of functional consequences involved in this neutrophil hypoxic survival phenotype, such as changes in cell movement and release of cytokines. The study of neutrophil apoptosis and clearance at low oxygen tensions is essential in probing diseases such as Chronic Obstructive Pulmonary Disease, where the degree of neutrophil persistence in the tissue corresponds with the severity of disease.

The aim of my project is to investigate the role of the neutrophil mitochondria in the context of neutrophil hypoxic survival and whether modulation of intracellular redox potential across different oxygen concentrations confers functional changes in the cell and the mitochondria, specifically. My project involves assessing mitochondrial function in normal and low oxygen through imaging the activity of a range of mitochondrial-specific functional dyes. I will also be using Surface Enhanced Raman Spectroscopy (SERS) to measure intracellular redox at different oxygen tensions.

The collaborative, multi-discipline aspect of the Optima CDT appealed to me greatly when applying and throughout the project has been invaluable in merging biological, chemical and physical aspects of the project into coherent, cross-discipline experiments.

I joined the Centre for Doctoral Training in Optical Imaging in Sept 2014 aimed at developing fibre-based smartprobes and sensors for use in critically ill patients and am working the Bradley research team as well as being aligned to the EPSRC IRC Proteus. My research has two angles: (i). Creating nanoparticle-containing-polymers for use in SERS (surface-enhanced Raman spectroscopy) and (ii). Looking into developing optical labels for an enzyme involved in inflammation. This will involve synthesising and investigating small molecule inhibitors of human neutrophil elastase (HNE) and the use of SERS and fluorescence in its detection.
Having studied medicinal and biological chemistry throughout my undergraduate time, I have always enjoyed learning about the applications of chemistry, particularly in healthcare. I joined the CDT because it offered an excellent opportunity to be a part of applied research, and to learn about the stages involved in taking science from a lab scenario through to commercialisation.

Nobel metal nanoparticles have received a large amount of attention in recent years, as their biomedical applications become realised. Of the nanoparticles available, the gold nanoparticle has great potential for biosensing and cancer treatment applications.
One of the advantages of gold nanorods is that their optical properties lie in the far visible and near infrared. Coupled with their ability to be excited via two photon illumination and low cytotoxicity means that the gold nanorod can be used for non-invasive bio sensing applications. Another advantage of the gold nanoparticle is that they can be developed into radiosensitizers, which are able to increase the dose of radiation in radiotherapy. This allows for lower and safer levels of radiation to be used when performing radiotherapy.
The aims of the project is to develop gold nanorods for cancer detection and treatment. In collaboration with the Cancer research centre at Edinburgh’s Institute of Genetic and Molecular Medicine I aim to use zebrafish embryos as an in vivo model for testing these gold nanoparticle biosensors. Then working with the National Physics Laboratory, I aim to develop the nanorods into radiosensitisers.
In today’s world the boundaries between scientific disciplines are merging and it fills me with great pride knowing that with the Optima program I am training to help cross these disciplines and bring about discoveries that could not have been achieved before.

Ms Rachael Cameron

Cancer clinicians provide treatment to patients with the belief that they will be effective based on their diagnosis. Sadly treatments are not always as efficacious as we would hope for, and the underlying reason is generally unknown, as there is no way to directly image these drugs within a cell.
This project aims to elucidate the anticancer drug localisation within the cell, its retention time and metabolites, by attaching metal nanoparticles to the drug. This would help explain, by following downstream signalling pathways, why the treatment is failing. Additionally, it is hoped that the drug’s efficacy can be enhanced due to the concentrated delivery method of the drug to the cancer cells, by exploiting the large surface area of the nanoparticles. A decreased IC50 would have the obvious benefits of lessening any side effects of the medication and saving on treatment costs.
This will be investigated by creating 3D cell maps using a confocal Raman microspectrometer to conduct signal enhanced Raman spectrosocpy (SERS) of the drug-nanoparticle conjugate within the cell. To be complemented by reverse phase protein assays to characterise any changes in cancer cell signalling pathways to explain the biochemical effect and mechanism of action of the drug-nanoparticle conjugates.

The OPTIMA CDT programme has allowed me to retrain in a different area of science with attention to the applications of the research. This was made possible by the multidisciplinary team of medics, researchers and business experts, who run workshops from the first week of the PhD programme. They are supportive and help to broaden your horizons making you more employable. Towards the end of the four years, a three month work placement will differentiate you from others on the jobs market.

Cancer clinicians provide treatment to patients with the belief that they will be effective based on their diagnosis. Sadly treatments are not always as efficacious as we would hope for, and the underlying reason is generally unknown, as there is no way to directly image these drugs within a cell.
This project aims to elucidate the anticancer drug localisation within the cell, its retention time and metabolites, by attaching metal nanoparticles to the drug. This would help explain, by following downstream signalling pathways, why the treatment is failing. Additionally, it is hoped that the drug’s efficacy can be enhanced due to the concentrated delivery method of the drug to the cancer cells, by exploiting the large surface area of the nanoparticles. A decreased IC50 would have the obvious benefits of lessening any side effects of the medication and saving on treatment costs.
This will be investigated by creating 3D cell maps using a confocal Raman microspectrometer to conduct signal enhanced Raman spectrosocpy (SERS) of the drug-nanoparticle conjugate within the cell. To be complemented by reverse phase protein assays to characterise any changes in cancer cell signalling pathways to explain the biochemical effect and mechanism of action of the drug-nanoparticle conjugates.

The OPTIMA CDT programme has allowed me to retrain in a different area of science with attention to the applications of the research. This was made possible by the multidisciplinary team of medics, researchers and business experts, who run workshops from the first week of the PhD programme. They are supportive and help to broaden your horizons making you more employable. Towards the end of the four years, a three month work placement will differentiate you from others on the jobs market.

OPTIMA2015 Cohort

Our OPTIMA 2015 cohort have powered through their second year and they are ready to dive headfirst into third year. Next step is organising their placements! Find out more about their exciting projects here in their own words.

Ms Hazel Stewart

Surgery is one of the primary treatment options for cancer alongside chemotherapy and radiotherapy. While there are many imaging techniques that play important roles in preoperative cancer diagnostics, very few can be applied intraoperatively to aid surgeons in distinguishing tumour margins. Fluorescence techniques offer a less costly and less disruptive alternative to traditional imaging methods for surgery; however there are currently a limited number of fluorophores that have been FDA approved as fluorescence imaging contrast agents for use in fluorescence guided surgery.

Based in the Photophysics Group at Strathclyde, this project will involve the investigation of the properties of both intrinsic and extrinsic fluorophores that have been identified as potential candidates for use in fluorescence guided surgery. Further to this, the implementation of a liquid light guide based fluorescence system will be tested, and medical applications outside of cancer surgery will also be investigated for these fluorophores.

OPTIMA offers a unique opportunity to develop interdisciplinary skills. As my background has a strong focus on physics, this programme offered the perfect opportunity for me to develop my skills in areas such as biology and chemistry, whilst contributing to meaningful research.

Mr Tom Speight

Arguably the biggest global problem in medicine is the huge rise in antibiotic resistance. We use far too many antibiotics and it gives pathogens the opportunity to develop a resistance, eventually making the drugs against them useless. One of the reasons we’re overusing antibiotics is a lack of confidence in our current methods to diagnose infections, especially those in the lower airways of the lung such as pneumonia. There is a desperate need for a more novel way to assess these parts of the body when an infection is suspected, so clinicians can make a more informed, confident decision over what treatment is best.

I’m working as a member of the Proteus research group, who are aiming to overcome these problems by developing an optical fibre-based imaging system, to be used in hospitals to image deep into the lung in real-time and at the bedside. My research will focus on the development and validation of a library of “smartprobes” designed to label a range of cells, from pathogens to host immune cells. These probes emit a fluorescent light only upon interaction with their specific target such as bacteria, thereby lighting up these cells to be detected with our fibre-based imaging system. Our ability to image pathogens in patient’s lungs will allow us to determine what treatment is best for the individual, promoting a more personalised approach to medical treatment. What’s more, by labelling immune cells as well as bacteria, we will be able to image this interaction between host and pathogen, identifying any possible failures in a patient’s immune system.

Having chosen a related PhD here in Edinburgh, OPTIMA have welcomed me into their programme and allowed me to gain a unique PhD experience I’d struggle to find anywhere else.

Ms Anastasia Kapara

Estrogen receptor (ER), is a transcriptional factor which is over-expressed in a variety of different cancers, including breast cancer. Although the treatment against ER overexpression is improving with less side effects, drug resistance remains one of the major clinical issue.

Overall, the aim of the project is to use sophisticated and sensitive technologies to address the molecular imaging of ER expression in breast cancer models. Determining the alterations in ER expression in response to novel anticancer drugs against breast cancer will lead to more effective drug selection, lower possibility of treatment failure and a clinically meaningful improvement in outcomes. Future prospective studies may involve long term monitoring of breast cancer patients, who are on endocrine therapy, by using a combination of molecular biology and nanotechnology for less invasive, targeted and rapid therapeutic approaches.

The OPTIMA programme places emphasis on interdisciplinary research as it combines the study of molecular interactions and structural dynamics with the development of a complete scientific business profile. I am confident that this PhD will improve my background knowledge and will contribute to achieve my personal goals which are to continue in the research field of molecular diagnosis and modern therapeutics.

Ms Jee Soo (Monica) Kim

Multiple sclerosis (MS) is a chronic and complex debilitating neurological disorder caused by inflammation and the inability to repair the damage on myelin sheaths. Myelin sheaths are lipid-rich structures made by cells called oligodendrocytes in the central nervous system, i.e. the brain and spinal cord. These cells wrap around the axons of neurons, the key signalling cells of the nervous system, to provide nutritional support and allow fast signalling conduction. MS cost the European economy €14.6 billion in 2010 alone with 540,000 sufferers. Current treatments are focused on dampening the damage and not enhancing their repair. My project is aimed at using medical optical imaging to create a high-throughput drug screening platform to find drugs that will enhance the repair of myelin sheaths in MS.

I joined the CDT OPTIMA programme because of its multi-disciplinary aspect. Although science is divided into different disciplines (biology, chemistry, engineering, physics, IT,…), I believe the best research is conducted when multiple, or even all, scientific disciplines are brought together. My project is allowing me to bring my biomedical sciences background to study the disease MS while incorporating the technology and knowledge from multiple other scientific disciplines. In addition, the programme is allowing the learning and development of how to take scientific ideas and research from the lab into the real-world, where they have the potential to make important societal impact.

Surgery is one of the primary treatment options for cancer alongside chemotherapy and radiotherapy. While there are many imaging techniques that play important roles in preoperative cancer diagnostics, very few can be applied intraoperatively to aid surgeons in distinguishing tumour margins. Fluorescence techniques offer a less costly and less disruptive alternative to traditional imaging methods for surgery; however there are currently a limited number of fluorophores that have been FDA approved as fluorescence imaging contrast agents for use in fluorescence guided surgery.

Based in the Photophysics Group at Strathclyde, this project will involve the investigation of the properties of both intrinsic and extrinsic fluorophores that have been identified as potential candidates for use in fluorescence guided surgery. Further to this, the implementation of a liquid light guide based fluorescence system will be tested, and medical applications outside of cancer surgery will also be investigated for these fluorophores.

OPTIMA offers a unique opportunity to develop interdisciplinary skills. As my background has a strong focus on physics, this programme offered the perfect opportunity for me to develop my skills in areas such as biology and chemistry, whilst contributing to meaningful research.

Arguably the biggest global problem in medicine is the huge rise in antibiotic resistance. We use far too many antibiotics and it gives pathogens the opportunity to develop a resistance, eventually making the drugs against them useless. One of the reasons we’re overusing antibiotics is a lack of confidence in our current methods to diagnose infections, especially those in the lower airways of the lung such as pneumonia. There is a desperate need for a more novel way to assess these parts of the body when an infection is suspected, so clinicians can make a more informed, confident decision over what treatment is best.

I’m working as a member of the Proteus research group, who are aiming to overcome these problems by developing an optical fibre-based imaging system, to be used in hospitals to image deep into the lung in real-time and at the bedside. My research will focus on the development and validation of a library of “smartprobes” designed to label a range of cells, from pathogens to host immune cells. These probes emit a fluorescent light only upon interaction with their specific target such as bacteria, thereby lighting up these cells to be detected with our fibre-based imaging system. Our ability to image pathogens in patient’s lungs will allow us to determine what treatment is best for the individual, promoting a more personalised approach to medical treatment. What’s more, by labelling immune cells as well as bacteria, we will be able to image this interaction between host and pathogen, identifying any possible failures in a patient’s immune system.

Having chosen a related PhD here in Edinburgh, OPTIMA have welcomed me into their programme and allowed me to gain a unique PhD experience I’d struggle to find anywhere else.

Estrogen receptor (ER), is a transcriptional factor which is over-expressed in a variety of different cancers, including breast cancer. Although the treatment against ER overexpression is improving with less side effects, drug resistance remains one of the major clinical issue.

Overall, the aim of the project is to use sophisticated and sensitive technologies to address the molecular imaging of ER expression in breast cancer models. Determining the alterations in ER expression in response to novel anticancer drugs against breast cancer will lead to more effective drug selection, lower possibility of treatment failure and a clinically meaningful improvement in outcomes. Future prospective studies may involve long term monitoring of breast cancer patients, who are on endocrine therapy, by using a combination of molecular biology and nanotechnology for less invasive, targeted and rapid therapeutic approaches.

The OPTIMA programme places emphasis on interdisciplinary research as it combines the study of molecular interactions and structural dynamics with the development of a complete scientific business profile. I am confident that this PhD will improve my background knowledge and will contribute to achieve my personal goals which are to continue in the research field of molecular diagnosis and modern therapeutics.

Multiple sclerosis (MS) is a chronic and complex debilitating neurological disorder caused by inflammation and the inability to repair the damage on myelin sheaths. Myelin sheaths are lipid-rich structures made by cells called oligodendrocytes in the central nervous system, i.e. the brain and spinal cord. These cells wrap around the axons of neurons, the key signalling cells of the nervous system, to provide nutritional support and allow fast signalling conduction. MS cost the European economy €14.6 billion in 2010 alone with 540,000 sufferers. Current treatments are focused on dampening the damage and not enhancing their repair. My project is aimed at using medical optical imaging to create a high-throughput drug screening platform to find drugs that will enhance the repair of myelin sheaths in MS.

I joined the CDT OPTIMA programme because of its multi-disciplinary aspect. Although science is divided into different disciplines (biology, chemistry, engineering, physics, IT,…), I believe the best research is conducted when multiple, or even all, scientific disciplines are brought together. My project is allowing me to bring my biomedical sciences background to study the disease MS while incorporating the technology and knowledge from multiple other scientific disciplines. In addition, the programme is allowing the learning and development of how to take scientific ideas and research from the lab into the real-world, where they have the potential to make important societal impact.

Ms Kirsty Callan

The mineralocorticoid aldosterone plays a key role in sodium transport via the mineralocorticoid receptor (MR). Glucocorticoids and mineralocorticoids have similar affinity for the MR, which can result in overstimulation of the receptor since glucocorticoids are present at much higher levels. This problem is avoided by the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which deactivates glucocorticoids. However, mutations can cause a lack, or inactivity, of HSD2. Lack of HSD2 results in a condition known as the syndrome of apparent mineralocorticoid excess (SAME) which is usually fatal in childhood. Deficiency of the enzyme has been shown to cause salt-sensitive hypertension. Currently, there is no clinical diagnostic test for HSD2 levels.

Nanoparticles are particles with at least one dimension less than 100nm. They have unique optical properties which make them useful in diagnostics. In particular, they can be used to increase the sensitivity of Raman spectroscopy by adsorbing the sample onto nanoparticles resulting in an enhanced signal (surface enhanced Raman spectroscopy). Furthermore, they can be functionalised with recognition molecules, such as DNA, for specific detection.

The aim of my project is to develop an assay for the detection of HSD2 mRNA based on nanoparticles and Raman spectroscopy. I was drawn to the OPTIMA program as I believe that the multidisciplinary nature of the program makes it different from other PhD programs and will be invaluable for a career in research.

Ms Katie Ember

Cholangiocarcinoma is a cancer of the bile duct that also affects the liver. Very little is known about the molecular basis for the disease and it has an extremely low survival rate – 95% of cases are fatal within 5 years. However, this could be significantly improved by novel diagnostic technologies. Raman spectroscopy is an optical technique capable of discriminating between tissue samples based on their molecular composition. It has proven a promising tool for cancer diagnosis and surgery but has never been applied to cholangiocarcinoma. I’m working with both the Campbell group of the School of Chemistry and the Forbes group of the Centre for Regenerative Medicine to develop Raman spectroscopy as a new way for sensing cholangiocarcinoma early and accurately. Such a tool could be implemented in diagnosis, surgery and investigating the efficacy of therapeutic drugs on cholangiocarcinoma. It could also greatly assist the elucidation of the underlying biomolecular mechanisms of this disease.

Optical medical imaging is where biology, chemistry and physics converge, and I’ve always found it difficult to choose one of the three sciences to focus on – they are all equally fascinating and many new technologies are arising from the conjunction between them. The interdisciplinary nature of the OPTIMA programme means that there are endless opportunities to learn new techniques and ways to approach problems, and Edinburgh and Glasgow are both fantastic places to do a PhD!

Ms Clara Vergez

Cardiovascular disease is the leading cause of death worldwide. Heart attacks occur when a blood clot blocks the coronary artery, restricting blood flow to the heart muscle. Atherosclerotic plaques in the coronary artery walls cause heart attacks when they rupture and expose their pro-coagulant contents to the blood supply, forming a clot.

Research in the field currently focusses on detecting plaques which are prone to rupture (i.e. “vulnerable plaques”) in the hope that removing them from patients with coronary artery disease will lower their risk of heart attack. OCT (optical coherence tomography) is a relatively new medical imaging technique enabling precise visualisation of “vulnerable plaque” morphology (such as a thin fibrous cap, a lipid core, calcifications) in a similar way to ultrasound, using light instead of sound to create an image of the tissue. However, one key feature yet to be made visible with OCT is macrophage infiltration into the cap of the plaque.

Preliminary studies have shown that macrophage visualisation within plaques may be possible with OCT and my thesis project aims to enhance this visualisation. Along the course of my project I will be working on in vitro models (a model “phantom” artery and ex-vivo human arteries), in vivo animal models as well as a human clinical trial. If we can enhance the detectability of macrophages within atherosclerotic plaques with OCT we could potentially distinguish vulnerable plaques from non-vulnerable ones and thus vulnerable patients from non-vulnerable ones!

I came across OPTIMA completely by chance when I had not yet started my search for PhDs and I was hooked when I heard about their aims and ideals. Most importantly for me, all the projects having an optical medial imaging component are very clinically relevant and many boast a "bench to bedside" philosophy. The added interdisciplinary component is what makes this PhD program unique, perhaps more challenging but certainly fun! And finally the taught entrepreneurship component of the OPTIMA program teaches us the importance of knowing how to commercialise science, a invaluable skill for our future careers, whatever they may be...

Mr Jamie Scott

Granzyme B is the signature enzyme of choice for CD8+ T Cells in our immune systems response against foreign bodies. CD8+ T Cells form a major part of the adaptive immune system and without their effector activity we would succumb to many infections and diseases. The activity of these cells is kept under control by T regulatory cells (Tregs) which are able to suppress function of CD8+s when required, in order to prevent autoimmune diseases.

Patients suffering from cancer have the ability to draw large numbers of CD8+ cells with specificities to tumour antigens to the TM. Therefore, in theory, these T cells should be able to mediate clearance of malignant cells in much the same manner as invading microbes/bacteria. However, in cancer patients these T cells are unable to eradicate the tumour because of an increasing number of CD4+ CD25+ Foxp3+ Tregs found in the TM. As previously described, Tregs have the capability to suppress the immune system, however, in the presence of malignant cells they should not suppress the immune response to such an extent that tumours can thrive. As such, the increasing ratio of Tregs:CD8+ T cells results in a worse prognosis and leads to development of tumour tolerance rather than tumour clearance. However, crucial questions remain unanswered: 1) what are the specific signals / molecules that give rise to an elevated number of Tregs in the TM, and 2) how Tregs suppress CD8+ T cell cytotoxicity in vivo.

In order to answer these questions my research combines both organic chemistry and immunology through the development of a fluorescent probe specific for CD8+ T Cells by labelling Granzyme B. Through fluorescence imaging of CD8+ T Cells in the TM we hope to address some of the previously unanswered questions.

The mineralocorticoid aldosterone plays a key role in sodium transport via the mineralocorticoid receptor (MR). Glucocorticoids and mineralocorticoids have similar affinity for the MR, which can result in overstimulation of the receptor since glucocorticoids are present at much higher levels. This problem is avoided by the presence of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2) which deactivates glucocorticoids. However, mutations can cause a lack, or inactivity, of HSD2. Lack of HSD2 results in a condition known as the syndrome of apparent mineralocorticoid excess (SAME) which is usually fatal in childhood. Deficiency of the enzyme has been shown to cause salt-sensitive hypertension. Currently, there is no clinical diagnostic test for HSD2 levels.

Nanoparticles are particles with at least one dimension less than 100nm. They have unique optical properties which make them useful in diagnostics. In particular, they can be used to increase the sensitivity of Raman spectroscopy by adsorbing the sample onto nanoparticles resulting in an enhanced signal (surface enhanced Raman spectroscopy). Furthermore, they can be functionalised with recognition molecules, such as DNA, for specific detection.

The aim of my project is to develop an assay for the detection of HSD2 mRNA based on nanoparticles and Raman spectroscopy. I was drawn to the OPTIMA program as I believe that the multidisciplinary nature of the program makes it different from other PhD programs and will be invaluable for a career in research.

Cholangiocarcinoma is a cancer of the bile duct that also affects the liver. Very little is known about the molecular basis for the disease and it has an extremely low survival rate – 95% of cases are fatal within 5 years. However, this could be significantly improved by novel diagnostic technologies. Raman spectroscopy is an optical technique capable of discriminating between tissue samples based on their molecular composition. It has proven a promising tool for cancer diagnosis and surgery but has never been applied to cholangiocarcinoma. I’m working with both the Campbell group of the School of Chemistry and the Forbes group of the Centre for Regenerative Medicine to develop Raman spectroscopy as a new way for sensing cholangiocarcinoma early and accurately. Such a tool could be implemented in diagnosis, surgery and investigating the efficacy of therapeutic drugs on cholangiocarcinoma. It could also greatly assist the elucidation of the underlying biomolecular mechanisms of this disease.

Optical medical imaging is where biology, chemistry and physics converge, and I’ve always found it difficult to choose one of the three sciences to focus on – they are all equally fascinating and many new technologies are arising from the conjunction between them. The interdisciplinary nature of the OPTIMA programme means that there are endless opportunities to learn new techniques and ways to approach problems, and Edinburgh and Glasgow are both fantastic places to do a PhD!

Cardiovascular disease is the leading cause of death worldwide. Heart attacks occur when a blood clot blocks the coronary artery, restricting blood flow to the heart muscle. Atherosclerotic plaques in the coronary artery walls cause heart attacks when they rupture and expose their pro-coagulant contents to the blood supply, forming a clot.

Research in the field currently focusses on detecting plaques which are prone to rupture (i.e. “vulnerable plaques”) in the hope that removing them from patients with coronary artery disease will lower their risk of heart attack. OCT (optical coherence tomography) is a relatively new medical imaging technique enabling precise visualisation of “vulnerable plaque” morphology (such as a thin fibrous cap, a lipid core, calcifications) in a similar way to ultrasound, using light instead of sound to create an image of the tissue. However, one key feature yet to be made visible with OCT is macrophage infiltration into the cap of the plaque.

Preliminary studies have shown that macrophage visualisation within plaques may be possible with OCT and my thesis project aims to enhance this visualisation. Along the course of my project I will be working on in vitro models (a model “phantom” artery and ex-vivo human arteries), in vivo animal models as well as a human clinical trial. If we can enhance the detectability of macrophages within atherosclerotic plaques with OCT we could potentially distinguish vulnerable plaques from non-vulnerable ones and thus vulnerable patients from non-vulnerable ones!

I came across OPTIMA completely by chance when I had not yet started my search for PhDs and I was hooked when I heard about their aims and ideals. Most importantly for me, all the projects having an optical medial imaging component are very clinically relevant and many boast a "bench to bedside" philosophy. The added interdisciplinary component is what makes this PhD program unique, perhaps more challenging but certainly fun! And finally the taught entrepreneurship component of the OPTIMA program teaches us the importance of knowing how to commercialise science, a invaluable skill for our future careers, whatever they may be...

Granzyme B is the signature enzyme of choice for CD8+ T Cells in our immune systems response against foreign bodies. CD8+ T Cells form a major part of the adaptive immune system and without their effector activity we would succumb to many infections and diseases. The activity of these cells is kept under control by T regulatory cells (Tregs) which are able to suppress function of CD8+s when required, in order to prevent autoimmune diseases.

Patients suffering from cancer have the ability to draw large numbers of CD8+ cells with specificities to tumour antigens to the TM. Therefore, in theory, these T cells should be able to mediate clearance of malignant cells in much the same manner as invading microbes/bacteria. However, in cancer patients these T cells are unable to eradicate the tumour because of an increasing number of CD4+ CD25+ Foxp3+ Tregs found in the TM. As previously described, Tregs have the capability to suppress the immune system, however, in the presence of malignant cells they should not suppress the immune response to such an extent that tumours can thrive. As such, the increasing ratio of Tregs:CD8+ T cells results in a worse prognosis and leads to development of tumour tolerance rather than tumour clearance. However, crucial questions remain unanswered: 1) what are the specific signals / molecules that give rise to an elevated number of Tregs in the TM, and 2) how Tregs suppress CD8+ T cell cytotoxicity in vivo.

In order to answer these questions my research combines both organic chemistry and immunology through the development of a fluorescent probe specific for CD8+ T Cells by labelling Granzyme B. Through fluorescence imaging of CD8+ T Cells in the TM we hope to address some of the previously unanswered questions.

Mr Paul Cowling

In 2015, lung cancer killed more than 1.5 million people worldwide. Lung cancer is the second most common form of cancer, leaving only 15% of patients alive five years after diagnosis. One of the reasons for this harrowing statistic is that many people are not diagnosed until advanced stages of the disease, during which treatments for lung cancer become less effective. Therefore, new techniques for early stage diagnosis are needed to help increase the number of earlier diagnoses and improve patient outcome.

I am developing new diagnostic tools which will allow for earlier detection of lung cancer, using bio-orthogonal reactions (reactions that can take place inside cells without interrupting normal biological processes). These reactions can be targeted so that they only occur inside cancer cells. I am using fluorescent probes that will be activated, or "switched on", by these bio-orthogonal reactions to image lung cancer cells. The benefit of using fluorescent probes is that the optical light emitted can be quantified in real time to visualise tumours. These new diagnostic tools are non-invasive, faster and more cost effective than current methods.

The primary benefit of working in the OPTIMA CDT is that I am part of a collaborative network of people who are constantly exchanging ideas. In addition, exposure to courses within the Business School helps improve my understanding of how to translate ideas to products for the general public.

Ms Lana Woolford

My project is centred around the creation of a diagnostic tool for cervical cancer which is automated, inexpensive and based on the ‘molecular pathology’ of the samples used. This is to try and improve the timing and accuracy of diagnosis for patients, and also to reduce the burden of manual diagnosis for clinicians. The project will involve looking at two different methods of using the optical scattering technique Raman spectroscopy to analyse the biochemical makeup of cells from the cervix.

The first method is the global approach, where all the biochemical differences between normal and cancerous samples are considered. This will be done using wavelength-modulated Raman spectroscopy (WMRS) to probe the vibrational energy levels of molecules in the sample, and does not require any major sample preparation. The second method is the targeted approach, where a specific marker for the cancer in question (such as an increase in the production of a particular protein) is measured in each sample. This will be carried out using surface–enhanced Raman spectroscopy (SERS). The Raman signal enhancement is provided by metal nanoparticles which have been tagged with an antibody to the protein being studied. The intensity of the Raman peaks for these ‘functionalised nanotags’ correspond to the levels of the target in the sample. The project will also look at how the Raman spectra can be automatically collected from thousands of cells in the same sample. Hopefully the final tool will improve cervical cancer diagnosis for patients and healthcare services alike.

Mr Scott Hoffmann*

Ms Gillian Craig

Cancer is a major cause of death worldwide and the majority of deaths are due to diagnosis at advanced stages when the cancer has metastasised. There is the need for more efficient cancer screening methods to improve patient survival. Cancer cells have a very different gene expression from healthy cells therefore mRNA biomarkers would be of great use for early detection.

My project is based at the Photophysics department at the University of Strathclyde where I am working to develop gold nanorod probes for the detection of cancer specific mRNA. Nanotechnology is new and exciting interdisciplinary field that combines engineering, physics, chemistry, biology and medicine. It has a huge potential for medical applications in the diagnosis and personalised treatments of human diseases. Nanoparticles such as gold are of particular interest in biological imaging due to the unique optical properties they possess.

The project aims to design gold nanorods functionalised with a DNA sequence that is complementary to the target mRNA and will also be conjugated to a fluorophore. This creates a probe that will emit a fluorescent signal once bound to its target. Fluorescence techniques will be used to characterise the probe as well as imaging techniques to study the probe in a cellular environment. A gold nanorod imaging probe has the potential to provide a non-invasive blood sample test which could provide early diagnosis of aggressive cancers.

My background is in cancer biology and I wanted to stay in this area while learning new skills to apply research that is clinically relevant. I chose the OPTIMA programme because of the unique training it offers. The exposure to innovation and business processes as well as the clinical and industrial placements really appealed to me, as well as the collaborative aspect of the project. I believe taking expertise from different disciplines will greatly strengthen the project.

In 2015, lung cancer killed more than 1.5 million people worldwide. Lung cancer is the second most common form of cancer, leaving only 15% of patients alive five years after diagnosis. One of the reasons for this harrowing statistic is that many people are not diagnosed until advanced stages of the disease, during which treatments for lung cancer become less effective. Therefore, new techniques for early stage diagnosis are needed to help increase the number of earlier diagnoses and improve patient outcome.

I am developing new diagnostic tools which will allow for earlier detection of lung cancer, using bio-orthogonal reactions (reactions that can take place inside cells without interrupting normal biological processes). These reactions can be targeted so that they only occur inside cancer cells. I am using fluorescent probes that will be activated, or "switched on", by these bio-orthogonal reactions to image lung cancer cells. The benefit of using fluorescent probes is that the optical light emitted can be quantified in real time to visualise tumours. These new diagnostic tools are non-invasive, faster and more cost effective than current methods.

The primary benefit of working in the OPTIMA CDT is that I am part of a collaborative network of people who are constantly exchanging ideas. In addition, exposure to courses within the Business School helps improve my understanding of how to translate ideas to products for the general public.

My project is centred around the creation of a diagnostic tool for cervical cancer which is automated, inexpensive and based on the ‘molecular pathology’ of the samples used. This is to try and improve the timing and accuracy of diagnosis for patients, and also to reduce the burden of manual diagnosis for clinicians. The project will involve looking at two different methods of using the optical scattering technique Raman spectroscopy to analyse the biochemical makeup of cells from the cervix.

The first method is the global approach, where all the biochemical differences between normal and cancerous samples are considered. This will be done using wavelength-modulated Raman spectroscopy (WMRS) to probe the vibrational energy levels of molecules in the sample, and does not require any major sample preparation. The second method is the targeted approach, where a specific marker for the cancer in question (such as an increase in the production of a particular protein) is measured in each sample. This will be carried out using surface–enhanced Raman spectroscopy (SERS). The Raman signal enhancement is provided by metal nanoparticles which have been tagged with an antibody to the protein being studied. The intensity of the Raman peaks for these ‘functionalised nanotags’ correspond to the levels of the target in the sample. The project will also look at how the Raman spectra can be automatically collected from thousands of cells in the same sample. Hopefully the final tool will improve cervical cancer diagnosis for patients and healthcare services alike.

Cancer is a major cause of death worldwide and the majority of deaths are due to diagnosis at advanced stages when the cancer has metastasised. There is the need for more efficient cancer screening methods to improve patient survival. Cancer cells have a very different gene expression from healthy cells therefore mRNA biomarkers would be of great use for early detection.

My project is based at the Photophysics department at the University of Strathclyde where I am working to develop gold nanorod probes for the detection of cancer specific mRNA. Nanotechnology is new and exciting interdisciplinary field that combines engineering, physics, chemistry, biology and medicine. It has a huge potential for medical applications in the diagnosis and personalised treatments of human diseases. Nanoparticles such as gold are of particular interest in biological imaging due to the unique optical properties they possess.

The project aims to design gold nanorods functionalised with a DNA sequence that is complementary to the target mRNA and will also be conjugated to a fluorophore. This creates a probe that will emit a fluorescent signal once bound to its target. Fluorescence techniques will be used to characterise the probe as well as imaging techniques to study the probe in a cellular environment. A gold nanorod imaging probe has the potential to provide a non-invasive blood sample test which could provide early diagnosis of aggressive cancers.

My background is in cancer biology and I wanted to stay in this area while learning new skills to apply research that is clinically relevant. I chose the OPTIMA programme because of the unique training it offers. The exposure to innovation and business processes as well as the clinical and industrial placements really appealed to me, as well as the collaborative aspect of the project. I believe taking expertise from different disciplines will greatly strengthen the project.

Ms Dawn Gillies

I want to understand cancer cell and tumour development. I am working with different label-free imaging techniques in order to discover more information about cancer cells and their environment as they grow using real time analysis. I will develop a platform to perform analysis in vivo. This technology will be useful in a number of different fields including developmental biology, embryology, drug research, and surgery.

I applied to the OPTIMA CDT as I can benefit from interdisciplinary supervisors and research, and I can combine my PhD with training in business and entrepreneurship. It is especially useful in biomedical research as it can help make the translation from scientific research to a clinical device which can have a positive impact on public health.

Mr Adeel Shafi

My research is centred around making bubbles. Microbubbles to be precise, they are extremely small - roughly the same size as our red-blood-cells. What's special about these microbubbles is that they can improve the grey-scale contrast seen during ultrasound imaging. Whilst in circulation, microbubbles which are sonicated act by absorbing the acoustic energy causing them to resonate, the amount of resonance depends upon a number of factors such as the frequency, acoustic power and size/composition of the microbubbles. Whilst resonating, they increase the scattering and reflection of the ultrasound waves, the ultrasound system picks up this extra information and it helps create a much clearer real-time image as there is detailed anatomical information for interpretation due to the excited microbubbles.

As there is the ability to control microbubble behaviour in vivo; what I am trying to develop is microbubbles which can act as contrast agents to enhance diagnosis, but at the same time have specific molecules attached on their surface that can stick to specific markers of vascular disease. This, therefore, can help in providing early diagnostic information as well as opening avenues for therapeutics as microbubbles can be functionalised to try and "attack" these specific markers which promote disease.

To understand microbubbles and learn more about their properties and potential in molecular imaging, I will be characterising them using an optical imaging methodology prior to testing them in preclinical ultrasonic in-vitro and in-vivo settings. I am also working on developing a new optical methodology which can enhance future microbubble investigations in vitro, meaning the microbubbles I make will not only be targeted to specific markers of vascular disease, they will also be fluorescent.

I chose to do my PhD as part of the OPTIMA programme because of the inter-disciplinary research it so strongly promotes. For example, my project involves an in-depth mix of materials science, medical physics and molecular biology! Through OPTIMA I also receive business training in health innovation and entrepreneurship, which I feel is vitally important in this day and age as it is giving me skills which will help my career progress after my PhD; regardless of whether I stay in academia, "go-solo" or work in industry.

Ms Helen Titmarsh

Lung cancer is the most common cause of cancer related deaths worldwide and many patients live for less than 12 months after diagnosis. This is often because patients are diagnosed with advanced/late stage disease. It is challenging to improve survival times because the earliest stages of lung cancer are difficult to definitively diagnose using simple non-invasive tests. It is also difficult to determine the best treatment options for each individual patient.

The aims of my research are to validate pre-existing and novel imaging agents for lung cancer. This work, along with that of a large team of biologists, chemists, physicists and medical doctors has the potential to lead to exciting developments in how lung cancer patients are diagnosed. The overall aims of our team are the produce and test fluorescence and radioactive probes which can be administered to patients. These probes interact with parts of cancer cells causing them to 'light up' on tests such as PET scans. This information can help doctors to detect where cancers are in the body, how far the cancer has spread and might provide information about how best to treat each individual lung cancer patient.

Ms Helen Parker

Working as a member of the Proteus research group, which aims to develop minimally invasive fibre based optical imaging of pathologies in the distal lung at the bedside, allows me the exciting opportunity to apply optical fibre physics to an unmet clinical need.

My research focuses on improving the optics of a wide-field fibre microendoscopy imaging system which uses dual light emitting diodes (LEDs) to illuminate lung tissue and induce fluorescence in targeted fluorescent molecules resulting in disease-specific wide-field multiplexed molecular imaging.

One of the challenges I am currently working on involves overcoming the inherent limitations of multicore imaging fibres. A limiting factor of the imaging quality of an optical fibre is the coupling of light from one core to its neighbouring cores. While core to core coupling is observed in all multicore fibres, we are using data gathered from our own optical fibres developed at the University of Bath to enable post-processing methods which will computationally compensate for the cross-talk between cores observed in images. This will counteract loss of contrast and allow for a clearer image and enhanced data visualisation for clinicians.

Another technical challenge of detecting exogenous fluorophores (when molecular tracers are used that specifically bind to targets such as bacteria) in human lung tissue stems from the abundantly present elastin and collagen. Elastin and collagen are endogenous fluorophores with broad autofluorescence emission peaks, which complicate the visualisation of narrower and weaker signals from disease specific fluorophores. However, by taking advantage of these different spectra by equipping our widefield imaging system with spectroscopic functionality we hope to overcome the issue and enable better visualisation of pathologies.

I want to understand cancer cell and tumour development. I am working with different label-free imaging techniques in order to discover more information about cancer cells and their environment as they grow using real time analysis. I will develop a platform to perform analysis in vivo. This technology will be useful in a number of different fields including developmental biology, embryology, drug research, and surgery.

I applied to the OPTIMA CDT as I can benefit from interdisciplinary supervisors and research, and I can combine my PhD with training in business and entrepreneurship. It is especially useful in biomedical research as it can help make the translation from scientific research to a clinical device which can have a positive impact on public health.

My research is centred around making bubbles. Microbubbles to be precise, they are extremely small - roughly the same size as our red-blood-cells. What's special about these microbubbles is that they can improve the grey-scale contrast seen during ultrasound imaging. Whilst in circulation, microbubbles which are sonicated act by absorbing the acoustic energy causing them to resonate, the amount of resonance depends upon a number of factors such as the frequency, acoustic power and size/composition of the microbubbles. Whilst resonating, they increase the scattering and reflection of the ultrasound waves, the ultrasound system picks up this extra information and it helps create a much clearer real-time image as there is detailed anatomical information for interpretation due to the excited microbubbles.

As there is the ability to control microbubble behaviour in vivo; what I am trying to develop is microbubbles which can act as contrast agents to enhance diagnosis, but at the same time have specific molecules attached on their surface that can stick to specific markers of vascular disease. This, therefore, can help in providing early diagnostic information as well as opening avenues for therapeutics as microbubbles can be functionalised to try and "attack" these specific markers which promote disease.

To understand microbubbles and learn more about their properties and potential in molecular imaging, I will be characterising them using an optical imaging methodology prior to testing them in preclinical ultrasonic in-vitro and in-vivo settings. I am also working on developing a new optical methodology which can enhance future microbubble investigations in vitro, meaning the microbubbles I make will not only be targeted to specific markers of vascular disease, they will also be fluorescent.

I chose to do my PhD as part of the OPTIMA programme because of the inter-disciplinary research it so strongly promotes. For example, my project involves an in-depth mix of materials science, medical physics and molecular biology! Through OPTIMA I also receive business training in health innovation and entrepreneurship, which I feel is vitally important in this day and age as it is giving me skills which will help my career progress after my PhD; regardless of whether I stay in academia, "go-solo" or work in industry.

Lung cancer is the most common cause of cancer related deaths worldwide and many patients live for less than 12 months after diagnosis. This is often because patients are diagnosed with advanced/late stage disease. It is challenging to improve survival times because the earliest stages of lung cancer are difficult to definitively diagnose using simple non-invasive tests. It is also difficult to determine the best treatment options for each individual patient.

The aims of my research are to validate pre-existing and novel imaging agents for lung cancer. This work, along with that of a large team of biologists, chemists, physicists and medical doctors has the potential to lead to exciting developments in how lung cancer patients are diagnosed. The overall aims of our team are the produce and test fluorescence and radioactive probes which can be administered to patients. These probes interact with parts of cancer cells causing them to 'light up' on tests such as PET scans. This information can help doctors to detect where cancers are in the body, how far the cancer has spread and might provide information about how best to treat each individual lung cancer patient.

Working as a member of the Proteus research group, which aims to develop minimally invasive fibre based optical imaging of pathologies in the distal lung at the bedside, allows me the exciting opportunity to apply optical fibre physics to an unmet clinical need.

My research focuses on improving the optics of a wide-field fibre microendoscopy imaging system which uses dual light emitting diodes (LEDs) to illuminate lung tissue and induce fluorescence in targeted fluorescent molecules resulting in disease-specific wide-field multiplexed molecular imaging.

One of the challenges I am currently working on involves overcoming the inherent limitations of multicore imaging fibres. A limiting factor of the imaging quality of an optical fibre is the coupling of light from one core to its neighbouring cores. While core to core coupling is observed in all multicore fibres, we are using data gathered from our own optical fibres developed at the University of Bath to enable post-processing methods which will computationally compensate for the cross-talk between cores observed in images. This will counteract loss of contrast and allow for a clearer image and enhanced data visualisation for clinicians.

Another technical challenge of detecting exogenous fluorophores (when molecular tracers are used that specifically bind to targets such as bacteria) in human lung tissue stems from the abundantly present elastin and collagen. Elastin and collagen are endogenous fluorophores with broad autofluorescence emission peaks, which complicate the visualisation of narrower and weaker signals from disease specific fluorophores. However, by taking advantage of these different spectra by equipping our widefield imaging system with spectroscopic functionality we hope to overcome the issue and enable better visualisation of pathologies.

OPTIMA2016 Cohort

Our OPTIMA 2016 cohort have made it through their first year and they are ready to power into second year. Find out more about their exciting projects here in their own words.

Ms Nicole Barth

The clearance of apoptotic cells is critical for tissue homeostasis and for the timely resolution of inflammation. Our lab has recently developed a new class of fluorescent peptides with ~100-fold selectivity for apoptotic cells. These peptides label apoptotic neutrophils extremely rapidly and offer important advantages over Annexin V -the gold standard in detecting membrane alterations associated with apoptosis- for medical imaging, namely calcium-independent binding, small size facilitating the access to tissue and functional neutrality.

The dysregulation of neutrophil apoptosis is an important factor in the persistent inflammation associated with chronic obstructive pulmonary disease (COPD). Current diagnostic methods for COPD rely on relatively basic tests (e.g. spirometry), which are not always efficient and cannot provide detailed information of the inflammatory state of the lungs. The aim of this project is to optimize the application of our probes as new imaging tools for the efficient diagnosis of COPD. Furthermore, this new platform has the potential to become a rapid and high-throughput technology to assess the efficacy of potential new treatments for COPD in humans.

Nicole will be trained in different facets of Optical Medical Imaging, such as fluorescence imaging, probe development, immunology and pulmonary medicine. The project will involve training in biomedical and physical sciences, and Nicole will work in labs with complementary expertise: Vendrell (fluorescent probes), Dransfield (neutrophil biology) and Walmsley (neutrophil apoptosis and pulmonary medicine).

Ms Iona Hill

Over 9000 cases of brain cancer are diagnosed in the UK annually with over 5000 deaths occurring and a 10-year survival rate of only 14%. Therefore, there is an urgent need for new approaches to be developed to understand brain cancer development. This project will use a variety of advanced Raman techniques to image 3D in vitro brain tumour spheroid models to further understand the growth of brain tumour development at a single cell level within a 3D tumour model.

Understanding how specific single cells behave and change within a heterogeneous tumour microenvironment, which reflects cells within different proliferative populations and within normoxic and hypoxic tumour regions is required to understand the way that cells communicate and influence each other as the tumour grows. Most studies to date have been on the bulk tumour, sections of tumorous tissue or single cells on their own. Here we will characterise single cells within tumour models and assess how they change as the tumour spheroid develops. Isogenic cell models will be created by gene editing and used to define specific gene specific effects on 3D imaging. In addition we will investigate how these tumours are affected when they are treated with drugs and how they respond to this treatment as a tumour as a whole, and at a single cell level.

To do this we will use a unique combination of different advanced Raman techniques including Raman imaging, Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman (CARS) and surface enhanced Raman (SERS) to gain a unique chemical insight into how individual cancer cells behave within a tumour model. These techniques will allow collection of high-resolution chemical information in 3 dimensions.

Ms Helena Engman

Chemical reduction-oxidation (i.e. Redox) reactions provide crucial links between fundamental chemical processes of cells (energy production, protein folding and small molecular synthesis) and the processes that determine cell fate (activation of transcription factors, apoptosis, miRNA biogenesis, epigenetic modification of histones and DNA). The ability to sense Redox reactions in real-time within cells and cell compartments (nuclear, soluble cytoplasm and membranous organelles such as mitochondria) is vital to understanding how cellular identity and behaviour is regulated by both internal and external cues. Human embryonic and induced pluripotent stem cells constitute an unparalleled scalable and renewable source of differentiated cells for discovery and therapy. Induction, renewal and differentiation of these cells are controlled by genetic and epigenetic determinants.

This project will design and implement functionalised Redox nanosensors for Surface Enhanced Raman Spectroscopy (Campbell laboratory) to interrogate mechanisms by which cellular Redox reactions involving established and novel gene pathways modulate human pluripotency induction, self-renewal and differentiation. Insights gained will serve to innovate new methods and reagents to manufacture and qualify human pluripotent stem cells for discovery and therapy.

Ms Jessie-May Morgan

Neutrophilic inflammation is central to disease pathogenesis e.g. in chronic obstructive pulmonary disease, yet the mechanisms retaining neutrophils within tissues remain poorly understood. A major research focus of our group has been dissecting the pathways that regulate both neutrophil lifespan and retention within tissues. This work has led us to identify the importance of hypoxia in key neutrophil survival responses and furthermore how neutrophils can themselves express molecules that regulate their retention within the tissues. Common to both these functional responses is the potential for cytoskeletal rearrangement, yet this remains a poorly studied area.

Through collaboration with Gail McConnell at Strathclyde University we have the unique opportunity to use Super resolution microscopy techniques to interrogate changes in f-actin dynamics during neutrophil lifespan and death and its regulation both by hypoxia and tissue recruitment. Ultimately we hope this approach will identify novel therapeutic targets for neutrophil mediated inflammatory diseases.

The clearance of apoptotic cells is critical for tissue homeostasis and for the timely resolution of inflammation. Our lab has recently developed a new class of fluorescent peptides with ~100-fold selectivity for apoptotic cells. These peptides label apoptotic neutrophils extremely rapidly and offer important advantages over Annexin V -the gold standard in detecting membrane alterations associated with apoptosis- for medical imaging, namely calcium-independent binding, small size facilitating the access to tissue and functional neutrality.

The dysregulation of neutrophil apoptosis is an important factor in the persistent inflammation associated with chronic obstructive pulmonary disease (COPD). Current diagnostic methods for COPD rely on relatively basic tests (e.g. spirometry), which are not always efficient and cannot provide detailed information of the inflammatory state of the lungs. The aim of this project is to optimize the application of our probes as new imaging tools for the efficient diagnosis of COPD. Furthermore, this new platform has the potential to become a rapid and high-throughput technology to assess the efficacy of potential new treatments for COPD in humans.

Nicole will be trained in different facets of Optical Medical Imaging, such as fluorescence imaging, probe development, immunology and pulmonary medicine. The project will involve training in biomedical and physical sciences, and Nicole will work in labs with complementary expertise: Vendrell (fluorescent probes), Dransfield (neutrophil biology) and Walmsley (neutrophil apoptosis and pulmonary medicine).

Over 9000 cases of brain cancer are diagnosed in the UK annually with over 5000 deaths occurring and a 10-year survival rate of only 14%. Therefore, there is an urgent need for new approaches to be developed to understand brain cancer development. This project will use a variety of advanced Raman techniques to image 3D in vitro brain tumour spheroid models to further understand the growth of brain tumour development at a single cell level within a 3D tumour model.

Understanding how specific single cells behave and change within a heterogeneous tumour microenvironment, which reflects cells within different proliferative populations and within normoxic and hypoxic tumour regions is required to understand the way that cells communicate and influence each other as the tumour grows. Most studies to date have been on the bulk tumour, sections of tumorous tissue or single cells on their own. Here we will characterise single cells within tumour models and assess how they change as the tumour spheroid develops. Isogenic cell models will be created by gene editing and used to define specific gene specific effects on 3D imaging. In addition we will investigate how these tumours are affected when they are treated with drugs and how they respond to this treatment as a tumour as a whole, and at a single cell level.

To do this we will use a unique combination of different advanced Raman techniques including Raman imaging, Stimulated Raman Scattering (SRS), Coherent Anti-Stokes Raman (CARS) and surface enhanced Raman (SERS) to gain a unique chemical insight into how individual cancer cells behave within a tumour model. These techniques will allow collection of high-resolution chemical information in 3 dimensions.

Chemical reduction-oxidation (i.e. Redox) reactions provide crucial links between fundamental chemical processes of cells (energy production, protein folding and small molecular synthesis) and the processes that determine cell fate (activation of transcription factors, apoptosis, miRNA biogenesis, epigenetic modification of histones and DNA). The ability to sense Redox reactions in real-time within cells and cell compartments (nuclear, soluble cytoplasm and membranous organelles such as mitochondria) is vital to understanding how cellular identity and behaviour is regulated by both internal and external cues. Human embryonic and induced pluripotent stem cells constitute an unparalleled scalable and renewable source of differentiated cells for discovery and therapy. Induction, renewal and differentiation of these cells are controlled by genetic and epigenetic determinants.

This project will design and implement functionalised Redox nanosensors for Surface Enhanced Raman Spectroscopy (Campbell laboratory) to interrogate mechanisms by which cellular Redox reactions involving established and novel gene pathways modulate human pluripotency induction, self-renewal and differentiation. Insights gained will serve to innovate new methods and reagents to manufacture and qualify human pluripotent stem cells for discovery and therapy.

Neutrophilic inflammation is central to disease pathogenesis e.g. in chronic obstructive pulmonary disease, yet the mechanisms retaining neutrophils within tissues remain poorly understood. A major research focus of our group has been dissecting the pathways that regulate both neutrophil lifespan and retention within tissues. This work has led us to identify the importance of hypoxia in key neutrophil survival responses and furthermore how neutrophils can themselves express molecules that regulate their retention within the tissues. Common to both these functional responses is the potential for cytoskeletal rearrangement, yet this remains a poorly studied area.

Through collaboration with Gail McConnell at Strathclyde University we have the unique opportunity to use Super resolution microscopy techniques to interrogate changes in f-actin dynamics during neutrophil lifespan and death and its regulation both by hypoxia and tissue recruitment. Ultimately we hope this approach will identify novel therapeutic targets for neutrophil mediated inflammatory diseases.

Mr Craig Murdoch

Optical imaging of biological tissue in order to differentiate between cancerous and healthy tissue is an important part of cancer research. Photoacoustic imaging (PAI) overcomes one of the main limitations of optical imaging, namely the difficulty of the latter to image tissue samples of thickness greater than a few hundred micrometres. This is due to strong light scattering characteristic of biological tissue that leads to reduction in optical image contrast and resolution. PAI overcomes this problem by focusing laser light deep inside tissue samples, generating wideband acoustic waves (via an optical-thermal-mechanical process), which are detected ultrasonically and processed to generate an image. This project will investigate PAI to differentiate between cancerous and non-cancerous tissue. It will initially develop a photoacoustic imaging platform combining lasers, optics and acoustics, then apply this platform to characterise two PAI contrast approaches, both focused on cancer research.

Craig will join a multidisciplinary research team with extensive experience in optical imaging techniques and bespoke nanomaterials, and their application in cancer research. This is a challenging and rewarding project, which offers an exceptional research experience, providing training and transferable skills in biomedical optical engineering and imaging applications.

Ms Kristel Sepp

Stimulated Raman Scattering (SRS) allows the quantitative imaging of drug molecules within cells without the need for additional labels, or nanoparticle sensors as used in many other optical imaging technologies. [1] It provides Raman imaging with minimal spectral distortion and a quantitative output, allowing the intracellular concentrations of drug molecules to be accurately determined. Spectroscopically bioorthogonal labels, which are ideal for the application of this technique to the study of drug uptake by SRS, are found in many drugs that are in pre-clinical development or in clinical use in oncology. In this project we will image clinically relevant drugs by SRS and develop new instrumentation for high-throughput SRS activated cell sorting (SRS-ACS).

[1] W. J. Tipping, M. Lee, A. Serrels, V. G. Brunton, A. N. Hulme, Chem. Soc. Rev. 2016, Advance Article.

Mr Andrea Usai

Understanding how redox potential controls cell phenotype is a life and death matter since the pathways that control pro-survival signalling and programmed cell death (apoptosis) is regulated by redox potential. Understanding redox signalling is important in targeted drug development in cancer and is complicated by the technical difficulty of measuring redox potential distributions in single cells.

Imaging redox potential distributions in cells requires a combination of SERS (surface Enhanced Raman spectroscopy) measurements and fluorescence measurements but the spectral overlap between the SERS and fluorescence spectra makes them difficult to analyse.

One solution is to use the fact that the SERS spectrum is generated (almost) instantaneously and the fluorescence spectrum is generated a couple of nanoseconds later. By using a detector based on Single Photon Avalanche Diodes (SPADs) we can separate the spectra based on their time of arrival at the detector.

The project involves a combination of chemistry, cell biology and engineering/programming. The outputs of the project include an improved understanding of redox signalling in diseases such as cancer, the first use of SPADs for time resolved SERS imaging.

Ms Amelia Hallas-Potts

This project is to develop a new high definition ‘light sheet’ microscope, which will allow us to see cancer live in three dimensions and in fine detail. It will also allow us to test new drug compounds for cancer treatment by giving us a detailed picture of how cancer responds to treatment.

Optical imaging of biological tissue in order to differentiate between cancerous and healthy tissue is an important part of cancer research. Photoacoustic imaging (PAI) overcomes one of the main limitations of optical imaging, namely the difficulty of the latter to image tissue samples of thickness greater than a few hundred micrometres. This is due to strong light scattering characteristic of biological tissue that leads to reduction in optical image contrast and resolution. PAI overcomes this problem by focusing laser light deep inside tissue samples, generating wideband acoustic waves (via an optical-thermal-mechanical process), which are detected ultrasonically and processed to generate an image. This project will investigate PAI to differentiate between cancerous and non-cancerous tissue. It will initially develop a photoacoustic imaging platform combining lasers, optics and acoustics, then apply this platform to characterise two PAI contrast approaches, both focused on cancer research.

Craig will join a multidisciplinary research team with extensive experience in optical imaging techniques and bespoke nanomaterials, and their application in cancer research. This is a challenging and rewarding project, which offers an exceptional research experience, providing training and transferable skills in biomedical optical engineering and imaging applications.

Stimulated Raman Scattering (SRS) allows the quantitative imaging of drug molecules within cells without the need for additional labels, or nanoparticle sensors as used in many other optical imaging technologies. [1] It provides Raman imaging with minimal spectral distortion and a quantitative output, allowing the intracellular concentrations of drug molecules to be accurately determined. Spectroscopically bioorthogonal labels, which are ideal for the application of this technique to the study of drug uptake by SRS, are found in many drugs that are in pre-clinical development or in clinical use in oncology. In this project we will image clinically relevant drugs by SRS and develop new instrumentation for high-throughput SRS activated cell sorting (SRS-ACS).

[1] W. J. Tipping, M. Lee, A. Serrels, V. G. Brunton, A. N. Hulme, Chem. Soc. Rev. 2016, Advance Article.

Understanding how redox potential controls cell phenotype is a life and death matter since the pathways that control pro-survival signalling and programmed cell death (apoptosis) is regulated by redox potential. Understanding redox signalling is important in targeted drug development in cancer and is complicated by the technical difficulty of measuring redox potential distributions in single cells.

Imaging redox potential distributions in cells requires a combination of SERS (surface Enhanced Raman spectroscopy) measurements and fluorescence measurements but the spectral overlap between the SERS and fluorescence spectra makes them difficult to analyse.

One solution is to use the fact that the SERS spectrum is generated (almost) instantaneously and the fluorescence spectrum is generated a couple of nanoseconds later. By using a detector based on Single Photon Avalanche Diodes (SPADs) we can separate the spectra based on their time of arrival at the detector.

The project involves a combination of chemistry, cell biology and engineering/programming. The outputs of the project include an improved understanding of redox signalling in diseases such as cancer, the first use of SPADs for time resolved SERS imaging.

This project is to develop a new high definition ‘light sheet’ microscope, which will allow us to see cancer live in three dimensions and in fine detail. It will also allow us to test new drug compounds for cancer treatment by giving us a detailed picture of how cancer responds to treatment.

Ms Maria Panagopoulou

Extracellular vesicles (EVs) are subcellular, membrane-delimited particles, which are produced by cells in response to multiple stimuli, including those eliciting proliferation and death. EVs mediate intercellular communication and can transfer their cargoes, including proteins and genetic material between cells, endowing recipient cells with new functional properties. In the blood of cancer patients, tumour-derived EVs may carry potentially useful biomarkers. Using novel and powerful imaging techniques, this project aims to study the phenotype of EVs present in the circulation of cancer patients.

We will image EV membrane efficacy using fluorescence lifetime and polarization microscopy as monitors of membrane fluidity in terms of order parameter and microviscosity, using rotor probes such BODIPY and diphenyl polyenes in free and phospholipid forms. Furthermore, EVs will be characterized by cryo-transmission electron microscopy (cryoTEM). This technique will ensure the nanometre resolution imaging and study of the vesicles in their hydrated, close to native state. A new multi-channel imaging and spectroscopic platform combining various optical modalities (e.g. Raman, fluorescence, nanoparticle-enhanced detection) will also be developed for the high-throughput, point-of-care, analysis of individual EVs. Using in vitro and in vivo experimental models as well as patient samples, proof-of-principle studies will be performed in order to investigate the potential relationship between blood-borne EVs and cancer status.

The project will provide training in a multidisciplinary range of skills in a cutting-edge area of cancer research and the results have the potential to change the way cancer patients are monitored and treated in the future.

Mr Angus Marks

3D tissue models are better mimics of the tissue microenvironment in vivo than monolayer culture of cells. In this project Angus will develop a 3D model of liver (liver organoid) that can be imaged with both spatial and temporal resolution. The imaging studies will help us understand how different cell types condition their microenvironment, with a focus on how chemistry of the niche affects tissue performance and viability. We will carry out these studies using a combination of imaging methods including surface enhanced Raman spectroscopy (SERS) using optical nanosensors, Raman imaging and mass-spectroscopy imaging. Subsequently liver organoids and imaging techniques will be used to investigate the mode of action of drugs with a view to predicting their clinical efficacy. This will be performed in collaboration with Astra Zeneca, with a view to improving the efficiency of the drug development process.

Ms Sonia Rehman

Sonia will be selecting her project soon. Once she has, the details will be posted here.

Ms Joanna Long

The rise of Antimicrobial Resistance (AMR) is the biggest and most important challenge faced in modern medicine. Without improved diagnostics and a better understanding of infection, modern medicine will cease to exist and we are at risk of regressing to the pre- antibiotic era. Routine operations, cancer therapies and small infections will become life- threatening events. One of the world’s leading causes of infectious death, tuberculosis has now developed total drug resistance (TDR). It is vital that we develop imaging methodologies to establish the site and extent of infection and to accelerate the testing and development of novel therapeutics. We often treat patients for months and years (MDR and TDR TB) without methods to ensure TB treatment success.

This project will involve the biological and in vivo testing of optical/Gallium imaging agents that will enable a ‘shake and shoot’ approach to whole body molecular imaging. A smart, fast, cheap and clinically deployable molecular imaging approach with whole body and microscopic resolution combining whole body PET and near patient optical imaging. Joanna will evaluate performance in preclinical and in year 3/4, through established first-in-man capability in the grouping- into patients in the Edinburgh Tuberculosis Clinic.

Joanna will join an international network collaborating to develop this for the detection and monitoring of tuberculosis and bacterial infections – Pretoria (South Africa), Groningen (Netherlands) and a commercial enterprise (Theragnostics). Joanna will spend time in the Radiochemistry group in Groningen as well visits to Pretoria (South Africa).
Joanna will embed in the Pulmonary Molecular Imaging Group and also in the School of Chemistry. The industrial partnership with leading experts in PET/optical (Ian Wilson and Greg Mullen) will ensure exposure to the academic-industrial interface. In addition Joanna will sit in tuberculosis clinics in Edinburgh Royal Infirmary and receive extensive clinical exposure to tuberculosis including the management and treatment of multi-drug resistant tuberculosis.

Extracellular vesicles (EVs) are subcellular, membrane-delimited particles, which are produced by cells in response to multiple stimuli, including those eliciting proliferation and death. EVs mediate intercellular communication and can transfer their cargoes, including proteins and genetic material between cells, endowing recipient cells with new functional properties. In the blood of cancer patients, tumour-derived EVs may carry potentially useful biomarkers. Using novel and powerful imaging techniques, this project aims to study the phenotype of EVs present in the circulation of cancer patients.

We will image EV membrane efficacy using fluorescence lifetime and polarization microscopy as monitors of membrane fluidity in terms of order parameter and microviscosity, using rotor probes such BODIPY and diphenyl polyenes in free and phospholipid forms. Furthermore, EVs will be characterized by cryo-transmission electron microscopy (cryoTEM). This technique will ensure the nanometre resolution imaging and study of the vesicles in their hydrated, close to native state. A new multi-channel imaging and spectroscopic platform combining various optical modalities (e.g. Raman, fluorescence, nanoparticle-enhanced detection) will also be developed for the high-throughput, point-of-care, analysis of individual EVs. Using in vitro and in vivo experimental models as well as patient samples, proof-of-principle studies will be performed in order to investigate the potential relationship between blood-borne EVs and cancer status.

The project will provide training in a multidisciplinary range of skills in a cutting-edge area of cancer research and the results have the potential to change the way cancer patients are monitored and treated in the future.

3D tissue models are better mimics of the tissue microenvironment in vivo than monolayer culture of cells. In this project Angus will develop a 3D model of liver (liver organoid) that can be imaged with both spatial and temporal resolution. The imaging studies will help us understand how different cell types condition their microenvironment, with a focus on how chemistry of the niche affects tissue performance and viability. We will carry out these studies using a combination of imaging methods including surface enhanced Raman spectroscopy (SERS) using optical nanosensors, Raman imaging and mass-spectroscopy imaging. Subsequently liver organoids and imaging techniques will be used to investigate the mode of action of drugs with a view to predicting their clinical efficacy. This will be performed in collaboration with Astra Zeneca, with a view to improving the efficiency of the drug development process.

Sonia will be selecting her project soon. Once she has, the details will be posted here.

The rise of Antimicrobial Resistance (AMR) is the biggest and most important challenge faced in modern medicine. Without improved diagnostics and a better understanding of infection, modern medicine will cease to exist and we are at risk of regressing to the pre- antibiotic era. Routine operations, cancer therapies and small infections will become life- threatening events. One of the world’s leading causes of infectious death, tuberculosis has now developed total drug resistance (TDR). It is vital that we develop imaging methodologies to establish the site and extent of infection and to accelerate the testing and development of novel therapeutics. We often treat patients for months and years (MDR and TDR TB) without methods to ensure TB treatment success.

This project will involve the biological and in vivo testing of optical/Gallium imaging agents that will enable a ‘shake and shoot’ approach to whole body molecular imaging. A smart, fast, cheap and clinically deployable molecular imaging approach with whole body and microscopic resolution combining whole body PET and near patient optical imaging. Joanna will evaluate performance in preclinical and in year 3/4, through established first-in-man capability in the grouping- into patients in the Edinburgh Tuberculosis Clinic.

Joanna will join an international network collaborating to develop this for the detection and monitoring of tuberculosis and bacterial infections – Pretoria (South Africa), Groningen (Netherlands) and a commercial enterprise (Theragnostics). Joanna will spend time in the Radiochemistry group in Groningen as well visits to Pretoria (South Africa).
Joanna will embed in the Pulmonary Molecular Imaging Group and also in the School of Chemistry. The industrial partnership with leading experts in PET/optical (Ian Wilson and Greg Mullen) will ensure exposure to the academic-industrial interface. In addition Joanna will sit in tuberculosis clinics in Edinburgh Royal Infirmary and receive extensive clinical exposure to tuberculosis including the management and treatment of multi-drug resistant tuberculosis.

Mr Dominic Norberg

The dynamic and large datasets that are collected as part of pulmonary microendsocopy are challenging to analyse and also quantify. This project will deal with the development and deployment of signal processing and image analysis tools to objectively quantify fluoresecence and patterns in data generated through clinical trials. The student will work with both the clinical team at Edinburgh and work with the medical image computing group at UCL to develop novel and clinically deployable methods to aid clinical decision making and analysis.

The dynamic and large datasets that are collected as part of pulmonary microendsocopy are challenging to analyse and also quantify. This project will deal with the development and deployment of signal processing and image analysis tools to objectively quantify fluoresecence and patterns in data generated through clinical trials. The student will work with both the clinical team at Edinburgh and work with the medical image computing group at UCL to develop novel and clinically deployable methods to aid clinical decision making and analysis.

OPTIMA2017 Cohort

OPTIMA is looking forward to welcoming our new students in September 2017. Looking forward to meeting you all at Induction Week!

Programme

OPTIMA has two key elements to its USP:
Projects at the interface of medical and physical science
Bespoke training in healthcare innovation and entrepreneurship

Integrated Study

Unlike other four year programmes, we want the integrated study portion to constantly inform and educate our students throughout their time with us. All of our students have innovative projects using cutting-edge technology to solve some of the most pressing issues in medicine today. We want our students to understand and appreciate the innovative leaps they are making and be able to capitalise on their discoveries. This trains our students to have a "Heart for Science and a Head for Business". When you have an academic research base that is commercialisation-aware and has real world nous - innovations will be fast-tracked and the leap from bench to bedside becomes a highway for cutting-edge healthcare.

Some of the courses that make up the integrated study portion of OPTIMA include:

• Optical Medical Imaging Grand Challenge.
• 3 month Industrial Placement
• Innovation-Driven Entrepreneurship
• Translational Study - Innovation and Entrepreneurship Masterclass
• Ethics and Regulatory Processes in Translating Innovation from Bench to Man
• Technology Commercialisation Workshop
• Build your own microscope workshop

Research

OPTIMA students can choose from a range of exciting and innovative projects that breakdown the barriers between physics, chemistry, medicine and engineering.

Please see below for an example of the projects you can do with OPTIMA:

Molecular level imaging of the Alzheimer’s beta amyloids aggregation induced by glycation

Tuneable liquid crystal lasers for fluorescence-based retinal disease diagnostics.

Optimising beta cell transplantation in humans through polymer technology

Development of an algorithm for real-time ultrasound tissue differentiation in liver disease.

Supervisors: Dr Olaf Rolinski / Dr Shareen Forbes / Prof David Birch

Alzheimer’s disease is associated with the aggregation of the small peptides beta-amyloids (A) gradually forming toxic fibrillar structures in the brain tissue of the sufferer. Although A aggregation has been widely studied, the mechanisms underlying the formations of aggregates in vivo are still poorly understood. Sporadic occurrence of Alzheimer’s implies that in addition to the typical factors determining aggregation (temperature, pH, ionic strength, presence of denaturants), other processes must contribute to the onset and progression of the disease. One of such processes seems to be glycation of A peptides, i.e. their modifications by interactions with carbohydrates. We hypothesise that determining the presence of different glycation products, leading to faster amyloidosis, may help to identify those at increased risk of developing Alzheimer’s. Our experiments will be performed in vitro and our aim is to identify photophysically different glycation products in beta-amyloids and correlate these products with the slow and high rates of formation of amyloid aggregates which will be monitored by fluorescence. We will therefore determine if the process of glycation and fluorescence operate in tandem.
Through links with Sunnergos the biotechnology business development arm of the University of Edinburgh we will liaise with a number of drug companies to open up the field of small molecule testing. We may then test if there are compounds that prevent formation of these products of glycation and consequently amyloidosis. Such studies would inform in vivo testing of these small molecules and therefore pave the way to the new therapeutics.
In this project we will apply time-resolved fluorescence spectroscopy and imaging (fluorescence lifetime imaging microscopy - FLIM) to monitor the glycation-induced misfolding and aggregation of A peptides in vitro. If a strong correlation between glycation and aggregation is found, an in vivo approach will be also developed. Intrinsic fluorescence signals from both the fluorescent amino acids and the advanced glycation end products (AGEs) are sensitive to the changes in the local environments on the nm scale. This makes the intrinsic fluorescence an ideal non-invasive method for gaining information on structural changes in the amyloid assemblies during their glycation and early stages of aggregation in different models of biological environments. In the project we aim to initially use the new techniques for time- and spectrally-resolved intrinsic fluorescence measurements to detect the smallest changes in protein conformations. After achieving μm sizes during aggregation, the amyloid fibrils will be investigated by fluorescence lifetime imaging microscopy (FLIM).

Supervisors: Dr Philip Hands / Dr Toby Hurd / Dr Ann Wheeler / Prof Baljean Dhillon

This PhD research project will develop newly-emerging tuneable and highly-customisable liquid crystal laser
sources, and apply them to the field of fluorescence-based retinal imaging, for the detection of age-related
macular degeneration and other ophthalmic diseases.
Autofluorescent (or fluorescent-tagged) biomarkers such as lipofuscin, within the retinal pigment epithelium,
can be optically probed using lasers to search for ophthalmic medical abnormalities. Despite the potential
capabilities of this technique, its clinical adoption is somewhat limited, restricted to specialist laboratories.
Each fluorescent biomarker has its own specific optical absorbance range, and so medical equipment must
compromise between detection versatility (i.e. containing multiple lasers with different wavelengths, each
targeting a different marker, and hence be large, bulky and expensive), or portability (i.e. contain only a single
laser source addressing a single fluorophore, and hence be small and portable). Compromised systems must
also be built around the availability of existing light sources, which do not cover the full colour spectrum,
resulting in poor signal strength and signal ambiguity due to overlapping absorbances between multiple
fluorophores.
Newly-developed liquid crystal (LC) lasers use self-assembling chiral nanostructures to create tuneable laser
cavities only 10 μm thick, and when doped with organic dyes enable simple, highly efficient and customisable
laser emission over the visible spectrum (450-850 nm). They have great potential as small, low-cost,
switchable and tuneable light sources for medical imaging applications, thus eliminating the requirement to
compromise between versatility, portability and cost, and potentially enabling cheaper, smaller and more
effective diagnostics tools. Tuneable LC lasers can be designed to perfectly match the absorbance
requirements of the biomarkers, maximising detection capabilities. They also provide a simple route to
providing new modalities of detection, such as ratiometric imaging and fluorescence lifetime imaging,
through temporal control of rapidly changing pulsed wavelength patterns.
Working in collaboration with engineers, biomedical scientists, ophthalmic clinicians and a world-leading
microscopy manufacturer on a highly interdisciplinary project, the student will demonstrate a proof-ofconcept
system using LC lasers to perform clinically-relevant fluorescence imaging of the retina for disease
diagnostics. They will use cleanroom microfabrication, opto-mechanical and electro-optical approaches to
construct bespoke LC laser and microscope systems (with properties including tuneable wavelengths and
temporal control of single or multiple simultaneous beams). LC lasers will be designed to optimally probe
multiple common fluorescent retinal markers simultaneously, and their performance advantages compared
to conventional sources will be validated. Further investigations will also be made into the clinical
opportunities of techniques such as ratiometric imaging and fluorescence lifetime imaging, enabled by LC
lasers, to provide improved data to the field of point-of-care ophthalmic disease detection. Opportunities for
commercial development will also be explored, in collaboration with our industrial partners.

Supervisors: Dr Shareen Forbes / Prof Mark Bradley / Dr Marc Vendrell

In individuals with Type 1 diabetes, beta cells (within a cluster of cells termed islets) are destroyed by immune processes and individuals are left dependent on insulin injections. Islet transplantation in individuals with Type 1 diabetes stabilises blood glucose control, improves quality-of-life and can be life-saving. However, islets engraft poorly in the body and individuals rarely come off insulin injections; most recipients require islets from at least 2-3 donor pancreases which is problematic due to donor organ shortage. Strategies to increase islet engraftment, diminish inflammation post-transplant and find alternatives sources of insulin secreting cells are urgently required.

We propose to test a human beta cell line (EndoC-BH3) with a range of polymers incorporating different ligands – e.g. collagen and anti-inflammatory ligands. We will identify which polymers promote beta cell engraftment and beta cell function in vitro. Candidate polymers will then be selected, labelled with fluorescent probes (fluorophores) used to coat beta cells prior to transplantation into mice using the kidney capsule route initially and then the clinically relevant intra-hepatic route. This in vivo imaging will be undertaken at short term time points initially to allow us to determine stability, fate, function and safety of such polymer-beta cell interactions which is urgently required in this field.

Supervisors: Dr James Hopgood / Mr Damian Mole / Ms Dawn Gilles and Mr Paul Cowling / Dr Colin Campbell

Liver cancer is the second leading cause of cancer deaths worldwide in men and, the sixth in women: millions of people are affected. Liver cancer usually arises on a background of chronic liver disease, and worldwide, 80% of liver cancer cases are due to hepatitis B and C infection. Ultrasound is a widely available technique that can be used to scan the liver for tumours. Where the liver is scarred from hepatitis, or other causes, distinguishing between cancer tissue and scarring is difficult. This project will develop and refine better ways of processing ultrasound images to improve cancer detection rates.

The data analysis developed could be equally applicable to other modalities, such as optical resolution photoacoustic microscopy (OR-PAM). OR-PAM has recently been used in liver analysis, which shows strong textural structure.

Using imaging to study the immune response in eczema patient’s skin

A chemical optical imaging platform for the identification of synergistic drug-immunotherapy combinations in cancer

Development of innovative correlative imaging technology/probes to monitor tumour-stromal cell interaction in disease

Using advanced spectroscopic tools to probe the effects of radiotherapy in primary tissue tumour models.

Supervisors: Dr Richard Weller / Dr Anne Astier / Dr Alastair Wark

Atopic Dermatitis (AD) is a common and disabling condition characterised by immunological defects and barrier dysfunction of the skin. Ultraviolet radiation (UVR) is an effective therapy for AD, and has a number of immuno-regulatory functions. We have studied the UVR-induced immunoregulatory molecules vitamin D, nitric oxide and cis-UCA and shown specific regulatory effects of these compounds on human T cells cultured in vitro. We have identified a novel pathway that could be therapeutically targeted in AD patients by re-purposing of an existing class of drugs. The typical immune dysfunction of AD has been shown to induce barrier dysfunction in skin, which itself leads to inflammation and immune dysregulation in a positive feedback cycle. We hypothesize that targeting our novel pathway with licensed drugs applied topically or orally to restore immune dysfunction will improve barrier function of the skin. The project will include development of different optical imaging tools (e.g. Raman, fluorescence and multiphoton) to visualize the molecules/cells involved in UV-induced regulatory pathways in the skin and correlating this to in vitro analysis. 1st Supervisor Weller runs a specialist eczema clinic and using imaging techniques developed in this proposal plans to measure the effects of agents acting on our novel target on immune and barrier dysfunction in AD.

Supervisors: Dr Alan Serrels / Dr Marc Vendrell / Dr Stefan Symeonides / Prof Steve Anderton

While immunotherapy has shown great promise as a therapeutic approach in the treatment of cancer, it is often accompanied by severe immune-mediated side-effects and many patients still do not respond. Hence, there is a need to identify new combinations with improved efficacy and tolerability for translation to the clinic. This effort is hampered by the lack of good high-throughput in vitro assays for identification of optimal immunotherapy combinations. We will address this urgent need through development of a high-throughput imaging platform for screening combinations of drug-immunotherapies, in order to identify those that optimally reprogram the function of tumour infiltrating T-cells by restoring their cytotoxic activity.

The project will consist of three main aims: (1) generation of novel chemical probes that identify and report on the activation status of T-cells, (2) optimization of multi-well culture and high-content confocal imaging of tumour tissue slices, and (3) development of automated image analysis algorithms for rapid identification of efficacious combinations. This screening platform will provide a much needed route to rapid identification of drug-immunotherapy combinations for testing in the clinic.
The student will be trained in different facets of Optical Medical Imaging, such as fluorescence imaging, image analysis, immunology and molecular oncology. The project will involve training in biomedical and physical sciences, and the student will work in labs with complementary expertise: Serrels (advanced imaging, cancer immunology), Vendrell (fluorescent probes), and Symeonides (molecular oncology and clinical trials), Anderton (Immunology and industry partnership).  

Supervisors: Dr Binzhi Qian / Dr Ann Wheeler / Prof Alison Hulme

Here we propose to characterise a novel model of metastasis which faithfully mimics metastatic hormone refractory prostate cancer. We will do this using a novel Imaging Platform and, in collaboration with Andor technologies, investigate its utility for intravital imaging. Once characterised we will develop probes with allow correlative imaging between SRS-Raman and fluorescent microscopy to allow us to further investigate our findings in an in vivo context.

Supervisors: Dr Colin Campbell / Dr Duncan McLaren / Dr Bill Nailon / Prof David Harrison

This project is a collaboration between the School of Chemistry, Edinburgh Cancer Centre and NHS Lothian.

Radiotherapy remains one of the most common therapies in the treatment of cancer but many questions remain regarding the optimisation of its delivery.
This project will utilise Raman and Surface Enhanced Raman Spectroscopies to evaluate the effect of radiotherapy on tumour models maintained in microenvironments that mimic those typical of hard-to-treat tumours (e.g. low oxygen concentration). We will use both Raman and SERS to evaluate the effect of radiotherapy (building on recent preliminary findings, Camus et al, Analyst, 2016) on organotypic tissue models derived from primary tissue. External Beam Radiation will be delivered in the most clinically-relevant means possible (using a tissue phantom in a clinical linear accelerator (LINAC) system) and a range of treatment protocols that vary dose, fractionation and combination with drugs will be investigated to find the optimal means of delivering radiotherapy to maximise tumour death and minimise collateral toxicity. The student will experience a breadth of research and training opportunities including working with nanoparticles, developing spectroscopic/imaging techniques, culturing organotypic tissue models and delivering therapy in a clinical environment.

Imaging the cellular origins of neurodegenerative disease using fluorescent gold nanoclusters

Imaging retinal metabolic changes with spectroscopic optical coherence tomography

Super Resolution Raman spectroscopy

Miniaturised oblique light-sheet microscopy for imaging of cell-bacterial interactions in antimicrobial resistance

Supervisors: Dr Yu Chen / Prof Kathryn Ball / Prof David Birch / Dr Paul Mulheran

A fundamental understanding of abnormal protein oligomerization/aggregation is vital in determining the causes of, and developing therapeutics for, Parkinson’s disease and Alzheimer’s disease. At present most meaningful molecular-level research into neurodegeneration associated disease proteins is pursued with model compounds in solution rather than in cells due to the lack of suitable fluorescence probes. We propose to overcome this limitation by making a new type of probe based on fluorescent protein encapsulated gold nanoclusters (AuNCs). Fluorescent AuNCs not only have overall properties superior to conventional probes, but also maintain biofunctionality of native proteins. Building on our previously study on AuNCs in HSA, BSA and lysozyme, we propose to synthesize fluorescent AuNCs in α-synuclein (WT and G51D) to investigate their initial assembly, oligomerisation pathway(s) and environmental factors that influence the oligomer formation employing fluorescence anisotropy of AuNC and FRET. Fluorescence imaging of various oligomers and intermediate supramolecular assemblies will lay the groundwork to move the study into imaging in neuronal cell models. By combining in vitro mechanism with cell-based imaging we have the potential to reveal the onset of protein oligomerisation and test therapies for its early reversal.

Supervisors: Dr Pierre Bagnaninchi / Prof Baljean Dhillon / Dr Colin Campbell

Oxygen metabolism plays a central role in major eye diseases such as glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. Optical coherence tomography is an established clinical imaging modality to assess microstructural changes in retinal layers. It generally uses near infrared light to provide label-free deep imaging. In this proposal, we wish to explore in collaboration with Optos, a leading retinal imaging company, the potential of spectroscopic OCT to image retinal metabolic changes relevant to eye diseases.
The Ph.D. candidate will first develop a dual-modality OCT-fluorescence based on a spectral domain interferometer to facilitate its adoption to an existing instrument. Then she/he will use the new modality to image in depth (<2mm) molecular information from commercial fluorescent probes and pathological microstructure alterations from OCT in vitro. In addition, oxygen saturation measurements will be performed at each pixel of the 3D image by exploiting the crossover behavior of hemoglobin and oxyhemoglobin (HbO2) absorption coefficients around 800 nm. Novel metabolic signatures will be further investigated by Raman spectroscopy to help establish S-OCT findings. Finally, the Core Technology Research Group of Optos will help guide the project with direction on medical device compliance, retinal imaging and commercialisation.
The ability of S-OCT to generate depth-resolved fluorescence images (<2mm) of metabolic biomarkers will be validated by imaging stem-cell-based in vitro models of AMD developed by Prof. Baljean Dhillon’s team, and corroborated to fluorescent assays and Raman spectroscopy in Dr. Campbell’s lab. 3D mapping of oxygen saturation will be calibrated on bovine whole blood flow driven through microfluidic channels and correlated to blood analyser readings. The student will gain an interdisciplinary profile developing a smart diagnostic tool with physicists, clinicians and chemists to evaluate the system and push its translation into clinical diagnosis. She/he will benefit from the opportunity to undertake short internships at Optos to work on specific sub-projects .

Supervisors: Prof Stephen Marshall / Prof Duncan Graham / Prof Karen Faulds / Prof Chris Gregory

Conventional Confocal Raman microscopy is able to generate clear images of biological samples based on the molecular vibrations. The technique is a powerful one but the resolution in these images has historically been limited by the diffraction limit of light.
This means that any biological cell structures which exist at a smaller resolution than this limit are currently inaccessible by Raman Imaging.
Recent work between Departments of EEE and Chemistry at Strathclyde has demonstrated that it is possible to go beyond the diffraction limit and this project aims at further developing this super-resolution approach and applying it to biological samples to identify and differentiate sub-cellular structure with molecular detail.
By combining sophisticated state of the art digital image processing algorithms with highly performing Raman instrumentation on a key biological sample, we will demonstrate the ability of our approach to go well beyond current, commonly obtainable spatial resolution using a Raman microscope. We see this as a key technological development to provide a simple and easy to use tool for use in the life sciences. We also envision the application of this tool to bioimaging to open new lines of investigation currently unimaginable due to technical limitations.
The project will be initiated on samples – experimental and clinical – containing extracellular vesicles (EVs) as these subcellular structures hold much promise as diagnostic and therapeutic targets for a variety of diseases and are difficult to image by conventional means. The project will be extended to include imaging of additional cell/tissue structures of potential clinical as appropriate. The technology will allow imaging at a scale not previously accessible by Raman Spectroscopy but which can now be observed, with all of the medical benefits that follow.

Supervisors: Dr Ralf Bauer / Prof David Dockrell

The increase in antimicrobial resistance is predicted to be one of the severe healthcare threats in the developed and developing world, influencing the possibility to tackle an ever increasing breadth of infectious diseases. Real-time 3D imaging of cell-bacterial interactions will allow monitoring of development pathways to help quantify mechanisms of antimicrobial resistance.
To create this capability, the proposed project is looking to develop custom, miniaturised, high resolution, oblique light-sheet microscopes using active micro-optical devices and high resolution 3D-printing and apply these systems in determining bacteria and mitochondrial co-localisation. Light sheet microscopy allows for fast 3D imaging with low phototoxicity, enabling the possibility of tracking developments over a wide range of time scales, with the miniaturisation potential being realised using optical Microelectromechanical Systems (MEMS) and high resolution 3D-printing. The novelty of the project is both in the miniaturisation of the imaging modality, as well as in the application to develop personalized diagnostic approaches to aid personalised therapeutic targeting to comabat infections. The aim is a cost-effective imaging system development of a new fluorescence based imaging tool tailored for medical research of in-vitro antimicrobial resistance host-pathogen interaction pathways that will be applicable to a range of settings, including those encountered in LMIC.

Genetic and chemical engineering of a modulatable and traceable human pluripotent cell derived mesenchymal stem cell platform for treatment of peritoneal inflammation

Optical Imaging and Optical Mediated Destruction of Bacteria

Supervisors: Dr Paul De Sousa / Prof Alison Hulme / Dr Vasileios Koutsos / Prof Jeremy Hughes

Inflammation & tissue damage are consequences of all infectious, inflammatory, degenerative or neoplastic disease for which stem cell based therapies offer complex reparative solutions. Mesenchymal stem cells (MSCs) have capability to modulate host immune response and promote tissue regeneration in a micro environmentally dependent manner. Age-associated decline in tissue reparative capabilities potentially make pluripotent human embryonic stem cell (hESC) derived MSC a superior “off the shelf” allogeneic therapeutic resource, also benefiting from pluripotent stem cell advantages of being more renewable, scalable and amenable to genetic modification.

In this project, we will develop and validate in vitro a strategy to both image and modulate the anti-inflammatory potency of a hESC derived MSC. We will apply gene-editing technology to a clinical grade hESC line to make a drug (doxycycline) inducible fusion protein coupled to a surface protein central to the production of a highly immunosuppressive factor which can be imaged. HESC-MSC fusion protein expressing cells will be characterised for canonical MSC-phenotype markers, genetic integrity, response to inflammatory cytokines, and cell membrane biophysical properties +/- doxycycline induction. The fluorescence reporter would permit real-time assessment of immunosuppressive factor expression, and by association immunosuppressive potency, in vitro in response to micro environmental manipulation and to tracking immunosuppressive MSCs in vivo in body tissues/cavities amenable to laparoscopic assessment.

Supervisors: Prof Mark Bradley / Prof David Dockrell / Dr Kev Dhaliwal

The project brings together the skills of synthetic chemistry, peptide chemistry and fluorophores with medicine and microbiology to target the antimicrobial resistance agenda agenda. It is all about targeting the binding and identification of bacterial infections using optical medical imaging techniques – but then does something about it – using light as the killing mechanism. The project sits between chemistry and medicine - targeting common bacteria before moving onto using clinical isolates.

Apply

OPTIMA will train 60 students in total.
Now is the chance for you to join the growing OPTIMA team

Join us

OPTIMA is looking for students ready for a PhD programme with a difference.

We need biologists, clinicians (medical / veterinary / dental), chemists, physicists and engineers to help us achieve a critical mass of trainee scientists ready for interdisciplinary research and bound for innovation.

The race is on to find the high-flying prospective PhD students for OPTIMA 2018.

Format

If you would like to apply to OPTIMA please submit a cover letter and a full up-to-date C.V. with names and addresses of two academic referees.

The cover letter should clearly state your eligibility and why you are interested in applying for a studentship with OPTIMA.

Send applications to imaging.cdt@ed.ac.uk

Please note OPTIMA studentships are subject to Research Council funding eligibility criteria. We do have a limited number of studentships for which EU nationals can apply. OPTIMA studentships cover fees and stipend for four years

OPTIMA cannot support tuition fees for overseas students but welcome applications from self-funding international students.

Deadlines

Applications are now open for joining OPTIMA in September 2018:

OPTIMA is looking to recruit students for projects in the theme of Optical Medical Imaging.

4 year PhD with integrated study programme in Healthcare Innovation and Entrepreneurship including 3 month industry placement

For further information – contact:

Dr Jean O’Donoghue (OPTIMA Manager)

j.odonoghue@ed.ac.uk

Industry Partners

One of the strengths of OPTIMA is its strong links to the business community via its industrial partners.

BioQuarter

"This CDT perfectly aligns with our vision to support and foster innovation and entrepreneurial skills in science related to healthcare. We urgently need to expand our base of scientific entrepreneurs who understand the process and real human value of commercialization to deliver improvements in healthcare."
Dr Mike Capaldi, Commercialisation Director

Entrepreneurial Spark

"Entrepreneurial Spark enthusiastically supports ... CDT in Optical Medical Imaging. We would be pleased to host placement students.. The students would be constantly networking with entrepreneurs, financiers, support firms, policy makers and business experts"
Lucy-Rose Walker, Co-founder and Chief Solutions Officer

Royal Society of Edinburgh

"The RSE would offer the student an opportunity to work within our Policy Advice Unit, which provides public policy advice to the Scottish Government, the UK Government and the EU....we are excited by the interdisciplinary, translational training program that you have put together"
Dr Bristow Muldoon, Head of Policy Advice

NPL

"The National Physical Laboratory (NPL) being the UK's National Measurement Institute, is a world-leading centre if excellence in developing and applying the most accurate measurement standards." "In it's effort to remain world-leading, the NPL is engaging with academia in line with its research priorities and interests" "The NPL is pleased to be able to support the..CDT in optical imaging" "Our interests are...strongly aligned with the theme of the...CDT"
Dr Alex Knight, Biotechnology Group - Analytical Science Division

"This CDT perfectly aligns with our vision to support and foster innovation and entrepreneurial skills in science related to healthcare. We urgently need to expand our base of scientific entrepreneurs who understand the process and real human value of commercialization to deliver improvements in healthcare."
Dr Mike Capaldi, Commercialisation Director

"Entrepreneurial Spark enthusiastically supports ... CDT in Optical Medical Imaging. We would be pleased to host placement students.. The students would be constantly networking with entrepreneurs, financiers, support firms, policy makers and business experts"
Lucy-Rose Walker, Co-founder and Chief Solutions Officer

"The RSE would offer the student an opportunity to work within our Policy Advice Unit, which provides public policy advice to the Scottish Government, the UK Government and the EU....we are excited by the interdisciplinary, translational training program that you have put together"
Dr Bristow Muldoon, Head of Policy Advice

"The National Physical Laboratory (NPL) being the UK's National Measurement Institute, is a world-leading centre if excellence in developing and applying the most accurate measurement standards." "In it's effort to remain world-leading, the NPL is engaging with academia in line with its research priorities and interests" "The NPL is pleased to be able to support the..CDT in optical imaging" "Our interests are...strongly aligned with the theme of the...CDT"
Dr Alex Knight, Biotechnology Group - Analytical Science Division

Roslin Cells

"we are continually seeking to improve the processes with which we manufacture cell therapy products. Disruptive technologies, such as Optical Medial Imaging, will undoubtedly be part of our future and accordingly I would welcome the opportunity to support the activities of the...Centre"
Aidan Courtney, CEO

Knowledge Transfer Network

"Thank you for the opportunity to partner in your proposal for a CDT in this area of Imaging and sensing. This field is one of significant strength in the UK, which we need to retain with appropriate skills, but we also need to be open to new imaging modalities and your proposal for Optical Medical Imaging is very timely. Our KTN is addressing Priority Areas across medical technologies, diagnostics in its broadest sense and stratified medicine in which optical imaging and sensing will play an important role."
Sue Dunkerton, Co-Director HealthTech and Medicines KTN

Harrison Goddard Foote

"HGF works with clients across a range of medical technologies, and optical medical imaging is a growing area interest. The technology area thus matches with areas of our business. We strongly encourage the focus upon business skills and translation that the CDT intends to incorporate into its studies; it is in this area that there would be an opportunity to work with you and the students."
Douglas Drysdale, Patents Director

Edinburgh Research and Innovation

"The mix of scientific and business skills that the...Centre's students would possess would be highly relevant to ERI in areas such as opportunity assessment, IP due diligence and business proposal development" "Furthermore, we anticipate that by being a partner we may have access to a stream of graduates who combine a strong physical science background with a level of business acumen"
Grant Wheeler, Head of Company Formation and Incubation

"we are continually seeking to improve the processes with which we manufacture cell therapy products. Disruptive technologies, such as Optical Medial Imaging, will undoubtedly be part of our future and accordingly I would welcome the opportunity to support the activities of the...Centre"
Aidan Courtney, CEO

"Thank you for the opportunity to partner in your proposal for a CDT in this area of Imaging and sensing. This field is one of significant strength in the UK, which we need to retain with appropriate skills, but we also need to be open to new imaging modalities and your proposal for Optical Medical Imaging is very timely. Our KTN is addressing Priority Areas across medical technologies, diagnostics in its broadest sense and stratified medicine in which optical imaging and sensing will play an important role."
Sue Dunkerton, Co-Director HealthTech and Medicines KTN

"HGF works with clients across a range of medical technologies, and optical medical imaging is a growing area interest. The technology area thus matches with areas of our business. We strongly encourage the focus upon business skills and translation that the CDT intends to incorporate into its studies; it is in this area that there would be an opportunity to work with you and the students."
Douglas Drysdale, Patents Director

"The mix of scientific and business skills that the...Centre's students would possess would be highly relevant to ERI in areas such as opportunity assessment, IP due diligence and business proposal development" "Furthermore, we anticipate that by being a partner we may have access to a stream of graduates who combine a strong physical science background with a level of business acumen"
Grant Wheeler, Head of Company Formation and Incubation

BBI Solutions OEM Ltd

"BBI recognize that imaging diagnostics promise to be the most powerful and rapidly growing sector within the in vitro diagnostics sector and we are keen to develop strategic relationships with leading academics within this space. We are always in need of scientists trained in the commercial and clinical context of our products and indeed this unique ‘skills’ offering is rarely available."
Dr Pete Corish, Head of Business Development

Renishaw Diagnostics

"The area of focus for this CDT is of direct interest to our company. We have been in contact with you in regard to the skill sets we see as being of interest to us as a company for the next generation of researchers and development of scientists who could potentially join us"
Dr Graeme McNay, Project Leader

Touch Bionics

"Touch Bionics enthusiastically supports OPTIMA. As a partner, we would be pleased to host placement students as they would have an unrivalled experience in the commercialisation of leading edge medical technologies. While for us, this partnership means access to top quality scientists and developing entrepreneurs.”
Hugh Gill, CTO

ST Microelectronics

"We view initiatives such as this, which boost the UK pool of highly knowledgeable and qualified engineers, as a strategic benefit to our industry. In addition the unique business and clinical awareness that these graduates will have will bring e a major boost to the local 'skills pool'."
Lindsay Grant, Director - Imaging Division

"BBI recognize that imaging diagnostics promise to be the most powerful and rapidly growing sector within the in vitro diagnostics sector and we are keen to develop strategic relationships with leading academics within this space. We are always in need of scientists trained in the commercial and clinical context of our products and indeed this unique ‘skills’ offering is rarely available."
Dr Pete Corish, Head of Business Development

"The area of focus for this CDT is of direct interest to our company. We have been in contact with you in regard to the skill sets we see as being of interest to us as a company for the next generation of researchers and development of scientists who could potentially join us"
Dr Graeme McNay, Project Leader

"Touch Bionics enthusiastically supports OPTIMA. As a partner, we would be pleased to host placement students as they would have an unrivalled experience in the commercialisation of leading edge medical technologies. While for us, this partnership means access to top quality scientists and developing entrepreneurs.”
Hugh Gill, CTO

"We view initiatives such as this, which boost the UK pool of highly knowledgeable and qualified engineers, as a strategic benefit to our industry. In addition the unique business and clinical awareness that these graduates will have will bring e a major boost to the local 'skills pool'."
Lindsay Grant, Director - Imaging Division

Almac

“The aims of the Centre for Doctoral Training are of direct interest to Almac. In addition to training the next generation of molecular and physical sciences, in the context of clinically relevant projects, the training in business skills and entrepreneurship is particularly important. Developing PhD scientists with business acumen and an understanding of the commercial scientific environment is highly desirable and we support this initiative 100%.”
Dr Stephen Barr, President and MD for Almac Sciences

i2eye Diagnostics

“i2eye Diagnostics Ltd is pleased to support the CDT in Optical Medical Imaging. This scientific area represents an important technological field for innovation in health care as well as economic development. In addition we strongly encourage the training in business skills and translation that your CDT provides.”
Les Gaw, CEO

PA Consulting Group

"Optics and imaging are valuable capabilities which PA Consulting Group offers to its clients. They are also areas where it can be challenging to recruit graduates and early-career scientists with the appropriate depth of knowledge and skills, coupled with the right approach to working on fast-paced commercial projects and the ability to communicate effectively with senior clients. We are pleased that the CDT training programme has been designed to address these issues and believe it can make an important contribution to the development of these valuable skills."
Dr Mark Humphries, PA Management Group

GSK

"the combination of excellence in physical sciences married with entrepreneurial training and clinical awareness make this a unique and fertile training opportunity"
Dr Malcolm Skingle, Director - Academic Liaison

“The aims of the Centre for Doctoral Training are of direct interest to Almac. In addition to training the next generation of molecular and physical sciences, in the context of clinically relevant projects, the training in business skills and entrepreneurship is particularly important. Developing PhD scientists with business acumen and an understanding of the commercial scientific environment is highly desirable and we support this initiative 100%.”
Dr Stephen Barr, President and MD for Almac Sciences

“i2eye Diagnostics Ltd is pleased to support the CDT in Optical Medical Imaging. This scientific area represents an important technological field for innovation in health care as well as economic development. In addition we strongly encourage the training in business skills and translation that your CDT provides.”
Les Gaw, CEO

"Optics and imaging are valuable capabilities which PA Consulting Group offers to its clients. They are also areas where it can be challenging to recruit graduates and early-career scientists with the appropriate depth of knowledge and skills, coupled with the right approach to working on fast-paced commercial projects and the ability to communicate effectively with senior clients. We are pleased that the CDT training programme has been designed to address these issues and believe it can make an important contribution to the development of these valuable skills."
Dr Mark Humphries, PA Management Group

"the combination of excellence in physical sciences married with entrepreneurial training and clinical awareness make this a unique and fertile training opportunity"
Dr Malcolm Skingle, Director - Academic Liaison

Engage

OPTIMA does not exist in a vaccuum. If you like what you see and want to know more - please, engage with us.

Prospective students

If you are thinking of pursuing a PhD and are interested in what OPTIMA has to offer, please get in touch

Dr Jean O'Donoghue
OPTIMA Project Manager

Phone: 0131 242 3343 /0131 650 4812
Email: j.odonoghue@ed.ac.uk

You can also catch up with us on Facebook and Twitter

Industry

We are interested in expanding our list of industrial partners and creating the links that can help our students appreciate the entrepreneurial drive and innovative spirit present in Scotland and the UK as a whole and learn how to become the scientific entrepreneurs of the future.

Some of the ways in which our industrial partners can engage with us are

• Collaborating on research projects
• Hosting OPTIMA students on 3-month placements
• Participating in OPTIMA training events

For more information contact:

Dr Jean O'Donoghue or Dr Kirsty Ross

Public

We want to expand our list of community partners and create the links that can help our students appreciate the impact their research will have on the world and learn how to become the confident communicators of the future.

Some of the ways in which our community partners can engage with us are

• Collaborating on outreach projects, such as art installations, demos, and visits
• Hosting OPTIMA students on 3-month placements
• Participating in OPTIMA outreach events

For more information contact:

Dr Kirsty Ross (OPTIMA Outreach Officer)
Phone: 0141 444 7042
Email: kirsty.ross@strath.ac.uk

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