Graduate Research Prize Winners 2013
After completing my studies for a BA in Biological Sciences at Oxford in 2008, I applied to read for a DPhil in Clinical Medicine under the supervision of Professor Lars Fugger, based at the Weatherall Institute of Molecular Medicine.
My project centred on the functional characterisation of a multiple sclerosis-associated genetic variant in the gene encoding the principle receptor for TNF (TNFR1). With the rest of the Fugger lab and as part of a multinational collaboration we demonstrated that this variant encodes a soluble version of the receptor capable of binding to TNF and antagonising TNF-mediated signalling.
This was striking in light of the results of clinical trials for the use of TNF antagonists in MS patients, in which neutralisation of TNF was associated with relapses and exacerbation of symptoms, and rare MS symptom-like side-effects in patients being treated with anti-TNF agents for the management of other inflammatory autoimmune diseases.
Thus we provided a functional explanation for the association of a multiple sclerosis-associated variant with the disease and revealed a novel use for genetic association studies; to inform clinical practice.
The work was published in Nature, and was recommended by the Faculty of 1000. We received positive coverage in both national and international media (featuring on the BBC News and Spiegel websites).
I feel very lucky to have had the opportunity to work on such an interesting project, as part of such a fantastic team. I thoroughly enjoyed my time at Oxford and cannot recommend studying for a DPhil at the Nuffield Department of Medicine highly enough.
Gregory AP*, Dendrou CA*, Attfield KE, Haghikia A, Xifara DK, Butter F, Poschmann G, Kaur G, Lambert L, Leach OA, Prömel S, Punwani D, Felce JH, Davis SJ,Gold R, Nielsen FC, Siegel RM, Mann M, Bell JI, McVean G, Fugger L. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature. 2012 Aug 23;488(7412):508-11.
*Authors contributed equally to this work.