Graduate Research Prize Winners 2008
I studied for my A-levels at Hills Road sixth-form college in Cambridge and came to Merton College in 1998 for the Master of Biochemistry degree, which I passed with 1st class honours. I then moved to Linacre College to start my D.Phil with Professor Simon Davis in the Weatherall Institute of Molecular Medicine. I came to Oxford with encouragement of my teachers at sixth-form college, and I decided to stay on in Oxford for my postgraduate studies because it was clear that the university was at the cutting-edge of biomedical research and offered a great pathway into a career in academia.
The majority of my work in the Davis lab was focused on identifying new ways to probe the organisation of molecules at the T-cell surface. This led to the key finding that the antigen receptor on T cells is almost certainly monovalent at the cell surface, which constrains any models of how triggering of this essential receptor occurs. The development of the methodologies required to elucidate this has provided a new means to probe the stoichiometry of proteins in situ at the single-molecule level. Through an alternative strategy, we have added compelling data to show that the important class of G-protein coupled receptors are unlikely to be oligomeric within the plasma membrane, against the prevailing view of the field. Work by other groups has started to support our data.
My time in Oxford and the Nuffield Dept of Medicine gave me the opportunity to work on excellent and important projects and collaborate with scientists throughout Europe. The regular talks by researchers from in and outside Oxford provided a way to keep in touch with areas not directly related to my own work. I found this was the best way to put my research goals in the wider context, and it has helped me to identify new questions that need answering. This environment is suitable for anyone hoping to have a career in science or scientific publishing, and as a stepping stone for being successful in the best research institutes around the world.
I am now an HHMI Research Associate at UCSF funded by the Jane Coffin Childs Memorial Fellowship. This three-year postdoctoral position will be used to explore the molecular mechanisms by which lymphocytes make a committed decision to respond to antigen and whether fine-scale clustering of important adapter proteins is essential to maintain this signalling. After this position, I intend to return to the UK with a career development fellowship and consolidate the skills required to become an independent investigator.
- James JR, White SS, Clarke RW, Johansen AM, Dunne PD, Sleep DL, Fitzgerald WJ, Davis SJ, Klenerman D. Single-molecule level analysis of the subunit composition of the T cell receptor on live T cells. Proc Natl Acad Sci U S A. (2007) 104:17662-7.
- James JR, Oliveira MI, Carmo AM, Iaboni A, Davis SJ. A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods. (2006) 3:1001-6.
- Evans EJ, Esnouf RM, Manso-Sancho R, Gilbert RJ, James JR, Yu C, Fennelly JA, Vowles C, Hanke T, Walse B, Hünig T, Sørensen P, Stuart DI, Davis SJ. Crystal structure of a soluble CD28-Fab complex. Nat Immunol. (2005) 6:271-9.
Figure showing that energy transfer efficiency and acceptor/donor ratio have a hyperbolic relationship for constitutive (light and dark blue) and weak dimers (red), whereas for monomers (green, orange, yellow) it is constant. Against expectation, G-protein coupled receptors give the signature of monomers.