Professor Stephen Graham

Remodelling of membrane architecture and composition by viruses

Viral evasion of innate immunity

Research

Stephen is interested in understanding how viruses change the composition and architecture of intracellular membranes, and how they evade immune recognition by the host. His team studies this using a broad range of biochemical, biophysical and cell biology techniques, ranging from cell-based models of infection and proteomics to biophysical analysis and atomic-resolution structures of protein complexes. This research provides fundamental insights into virus biology and virus:host interactions that underpins the development of future anti-viral therapies and virus-based biologics.

Publications

Key publications:

T.H. Benedyk, V. Connor, E.R. Caroe, M. Shamin, D.I. Svergun, J.E. Deane, C.M. Jeffries, C.M. Crump, S.C. Graham (2022) Herpes simplex virus 1 protein pUL21 alters ceramide metabolism by activating the inter-organelle transport protein CERT. Journal of Biological Chemistry, in press [doi: 10.1016/j.jbc.2022.102589]
K.L. Nahas, V. Connor, K.M. Scherer, C.F. Kaminski, M. Harkiolaki^, C.M. Crump^, S.C. Graham^ (2022) Near-native state imaging by cryo-soft-X-ray tomography reveals remodelling of multiple cellular organelles during HSV-1 infection. PLoS Pathogens, 18: e1010629 [doi: 10.1371/journal.ppat.1010629]
W.N.D. Gao, C. Gao, J.E. Deane, D.C.J. Carpentier, G.L. Smith, S.C. Graham (2022) The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds. Journal of General Virology 103: 001716 [doi: 10.1099/jgv.0.001716]
T.H. Benedyk, J. Muenzner, V. Connor, Y. Han, K. Brown, K.J. Wijesinghe, Y. Zhuang, S. Colaco, G.A. Stoll, O.S. Tutt, S. Svobodova, D.I. Svergun, N.A. Bryant, J.E. Deane, A.E. Firth, C.M. Jeffries, C.M. Crump^, S.C. Graham^ (2021) pUL21 is a viral phosphatase adaptor that promotes herpes simplex virus replication and spread. PLoS Pathogens, 17: e1009824 [doi: 10.1371/journal.ppat.1009824]
C. Conceicao*, N. Thakur*, S. Human, J.T. Kelly, L. Logan, D. Bialy, S. Bhat, P. Stevenson-Leggett, A.K. Zagrajek, P. Hollinghurst, M. Varga, C. Tsirigoti, M. Tully, C. Chiu, K. Moffat, A.P. Silesian, J.A. Hammond, H.J. Maier, E. Bickerton, H. Shelton, I. Dietrich, S.C. Graham, D. Bailey (2020) The SARS-CoV-2 Spike protein has a broad tropism for mammalian ACE2 proteins. PLoS Biology 18: e3001016 [doi: 10.1371/journal.pbio.3001016]
T.K. Soh*, C.T.R. Davies*, J. Muenzner*, L.M. Hunter, H.G. Barrow, V. Connor, C.R. Bouton, C. Smith, E. Emmott, R. Antrobus, S.C. Graham^, M.P. Weekes^, C.M. Crump^ (2020) Temporal Proteomic Analysis of Herpes Simplex Virus 1 Infection Reveals Cell-Surface Remodeling via pUL56-Mediated GOPC Degradation. Cell Reports, 33: 108235 [doi: 10.1016/j.celrep.2020.108235]
B.G. Butt, D.J. Owen, C.M. Jeffries, L. Ivanova, C.H. Hill, J.W. Houghton, M.F. Ahmed, R. Antrobus, D.I. Svergun, J.J. Welch, C.M. Crump, S.C. Graham (2020) Insights into herpesvirus assembly from the structure of the pUL7:pUL51 complex. eLife, 9: e53789 [doi: 10.7554/eLife.53789]