I am a 1st year PhD student interested in the roles intracellular signalling play in the pathogenesis of various disease states. I started at Warwick in 2013 having gained a place on the Interdisciplinary Biomedical Research (IBR) programme. Prior to this I was a student at the University of East Anglia, where I graduated with a 1st in Biomedicine.
Having undertaken a degree with a focus upon human disease and the processes that directly attribute to these pathologies, I quickly learnt that I have a keen interest in cellular signalling. Through the perturbation of these finely balanced pathways multiple diseases can occur. Through general study of signalling systems I focused in on receptor serine/threonine kinases (TGFβ) and G protein-coupled receptors (GPCRs).
With this interest in mind I started applying for PhDs in related fields, which lead me to the IBR programme on offer at Warwick. This offered the chance to learn new skills out of my field of comfort through undertaking a 1 year MSc in interdisciplinary research, then to carry on and undertake a PhD in my chosen field. As part of the MSc component I completed two 12 week mini-research projects;
- Developing a strategy for purification of the helicase CMG and DNA polymerase epsilon
- Using Saccharomyces cerevisiae to analyse the pharmacology of the adenosine A3 receptor.
These were undertaken in the laboratories of Drs Giacomo De Piccoli, and Graham Ladds. Through completing these short projects I was able to obtain knowledge and practical skills that will help me throughout my PhD.
I am supervised by Dr Graham Ladds, whos laboratory I work in, at the Department of Pharmacology (University of Cambridge), where I undertake all my research and shall complete my PhD.
G protein-coupled receptors (GPCRs) are a major target for the pharmaceutical industry, with approximately 50% of all drugs targeting these receptors. GPCRs can be classified into 6 major families, A-F. Family B GPCRs, also know as the secretin-like receptors, are less numerous, containing only 16 members although these have, to date, received limited focus. One family B receptor group that has been show to play a major role in; diabetes, cardiovascular disease, bone disorders and alzheimers, are the calcitonin (CT) and calcitonin-receptor like (CLR) receptors. Both these GPCRs have been shown to associate with receptor activity-modifying proteins (RAMPs) giving rise to 6 distinct receptors. While we understand the molecular basis of these interactions very little, to date, is know regarding their signaling bias properties beyond activation of adenylate cyclase. In this project we are quantitating the extent of ligand-directed signaling bias and exploring mechanisms of desensitization for the CT family of receptors.
In this project we will specifically study the following processes:
1 - Association of RAMPs with the CT and CLR receptors.
2 - RAMP-CT and RAMP-CLR receptor trafficking to the plasma membrane.
3 - Quantitate the rate of receptor internalisation in response to different stimulating ligands.
4 - Determine the extent to which RAMPs modulate CT and CLR internalisation.
CT and CLR receptor pharmacology will initially be determined in Saccharomyces cerevisiae, and then continued using transfected mammalian cell lines.
This project is funded by the Medical Research Council .
I dot J dot Winfield at warwick dot ac dot uk