Amelia Hallas-PottsView profile/website
My project involves the development of a novel bio-assay to investigate the phenotype of an individual patient’s tumour. It has potential application in patient-specific diagnosis and personalised medicine including the direct measurement of individual patients’ tumour response to drug therapy.
Andrea UsaiView profile/website
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.
Angus MarksView profile/website
3D tissue models are better mimics of the tissue microenvironment in vivo than monolayer culture of cells. In this project I 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.
Craig MurdochView profile/website
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.
I have joined 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.
Dominic NorbergView profile/website
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 fluorescence and patterns in data generated through clinical trials.
I will work with both the clinical team at Edinburgh and with the medical image computing group at UCL to develop novel and clinically deployable methods to aid clinical decision making and analysis.
Helena EngmanView profile/website
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.
Iona HillView profile/website
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%. There is an urgent need for new approaches 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 I 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 I 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 I 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.
Jessie-May MorganView profile/website
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 I 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 I hope this approach will identify novel therapeutic targets for neutrophil mediated inflammatory diseases.
Joanna LongView profile/website
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. I 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.
I 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). I will spend time in the Radiochemistry group in Groningen as well visits to Pretoria (South Africa).
I will be embedded 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 I 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.
Kristel SeppView profile/website
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.
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 I will image clinically relevant drugs by SRS and develop new instrumentation for high-throughput SRS activated cell sorting (SRS-ACS)
Maria PanagopoulouView profile/website
Imaging blood-borne extracellular vesicles to improve cancer diagnosis and therapy.
Extracellular vesicles (EV) are small particles released
from cells. They are made up of a membrane with composition similar to that of
the cell membrane and also carry other cellular components. EV have a variety
of roles both in health and disease, mainly assisting communication between the
cells. Depending on the type of cells they have been secreted from, they have
special signatures molecules which can be used to identify their origin. In
cancer, we can detect EV in the blood circulation and the analysis of their
molecular signatures can be an indication of cancer, thus providing us with a
Nicole BarthView profile/website
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.
I 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 I will work in labs with complementary expertise: Vendrell (fluorescent probes), Dransfield (neutrophil biology) and Walmsley (neutrophil apoptosis and pulmonary medicine).
Sonia RehmanView profile/website
Optical imaging for key targets in cancer.