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Chris Lindsay

BHF CRE Cardiovascular Medicinal Chemistry Graduate Student

Project: A chemical biology approach to investigate statin-induced dysfunction of ryanodine receptor channels: A means to widen the statin therapeutic index

Supervisors: Professor Angela Russell and Professor Rebecca Sitsapesan

Biography

I studied for my undergraduate MChem degree here in Oxford, at St Hilda’s College. A unique part of the Oxford course is that the fourth year is devoted entirely to a research project, with no lectures or tutorials. I joined Prof Chris Schofield’s lab for my part II project, where I worked on the synthesis of novel nucleoside phosphoramidites aiming to develop a fluorescence based assay for a human 2OG oxygenase called TET2, thought to be implicated in cancer. This was my first exposure to research which I found to be exciting, interesting and extremely motivating. I decided that I wanted to stay in research and began looking for DPhil programs.

I was attracted to the BHF DPhil in Cardiovascular Medicinal Chemistry, as the aspect of my masters research that I had most enjoyed was working on the boarder of chemistry and biology. In particular, the rotation projects were each shared between two labs, one in chemistry and the other in biology. This seemed like a great opportunity to experience work in as many different labs as possible, and make an informed choice about my DPhil project.

Rotation Project 1 (February – June)

I spent my first rotation working between Prof Angela Russell (chemistry) and Prof Rebecca Sitsapesan (pharmacology). The project was new and inspired by recent literature reports that statins, blockbuster drugs which are prescribed worldwide caused unregulated calcium release in muscle cells and were associated with a wide variety of muscle related side-effects. The Sitsapesan group are specialists in the study of ion channels and so I learnt various techniques to study ion channels using electrophysiology.  I also spent time synthesising a small molecule pharmacophore in the Russell group.

Rotation Project 2 (June – October)

For my second rotation I was split between Prof Darren Dixons lab (chemistry) and Dr Charles Redwood (Cardiovascular medicine). Unlike my first rotation, here I was picking up a project where a previous student had left off. The aim of the project was to develop a small molecule which could desensitise troponin C to Ca2+, as a potential treatment for hypertrophic cardiomyopathy.  When I started the project there were a number of molecules that were promising but had low potency and undesirable pharmacokinetic properties. We were able to synthesise a larger panel of compounds in the Dixon lab, which after testing in in-vitro assays revealed a highly potent compound that appeared to be much more active than any other previously tested.

I ultimately decided to return to my first rotation project for the remaining three years of my DPhil. The rotations were a great opportunity to learn new techniques, and gain experience of working in multiple different labs across disciplines.

Undergraduate degree:  MChem, University of Oxford

Studentship dates: September 2015 intake.