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.
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!