Our research
Viruses are expert cell biologists: they very efficiently convert cells to into virus production and dissemination factories while simultaneously avoiding detection by the host immune system. Cellular membranes are essential for these processes: they form contact sites between cells, they present triggers for the host immune system, and they are used to make new virus particles. We seek to understand the molecular mechanisms by which viruses remodel the composition and architecture of infected cells, with a focus on host membranes. We take a highly integrated approach, combining discovery science (proteomics) with high-quality molecular characterisation (structural biology and biophysics), computational biology (AI and molecular dynamics) and cell biology (microscopy and infection studies). Our work aims to define molecular mechanisms that link virus-induced changes in the cellular environment to disease phenotypes, providing the underpinning science for the design of future therapies.
Current research topics include:
- Physically deformation of host-cell membranes by herpesvirus proteins
- Virus-induced remodelling of cell junctions and adhesions
- Viral hijacking of host-cell phosphatases during infection
- Multi-modal imaging of herpesvirus infection
- Novel reagents to detect and prevent infection by Oropouche virus, a neglected RNA virus endemic to Latin America
- Novel methods to prevent evolution of resistance to antiviral drugs
Key Publications
- N.S. Barbosa, J.O. Concha, L.L.P. da Silva, C.M. Crump^, S.C. Graham^ (2023) Oropouche virus glycoprotein topology and cellular requirements for glycoprotein secretion. Journal of Virology, 97: e01331-22 [https://doi.org/10.1128/jvi.01331-22]
- 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 [https://doi.org/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 [https://doi.org/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 [https://doi.org/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 [https://doi.org/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 [https://doi.org/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 [https://doi.org/10.7554/eLife.53789]
Professor Stephen Graham
Principal Investigator
Group Members