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Department of Pathology

 
Atomic Virology

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 host membranes during infection. We take a highly integrated approach, combining discovery science (proteomics) with high-quality molecular characterisation (structural biology and biophysics) and cell biology (microscopy and infection studies). Our work aims to define molecular mechanisms that link virus-mediated membrane remodelling 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 attachment factors (focal adhesions)
  • Mechanisms and phenotypes of viral host-cell lipid transport modulation
  • Viral hijacking of host-cell phosphatases during infection
  • Novel reagents to detect and prevent infection by Oropouche virus, a neglected RNA virus endemic to Latin Americ

Key Publications

  • 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]
  • C. Gao, M.A. Pallett, T.I. Croll, G.L. Smith, S.C. Graham (2019) Molecular basis of cullin-3 (Cul3) ubiquitin ligase subversion by vaccinia virus protein A55. Journal of Biological Chemistry, 294: 6416–6429 [https://doi.org/10.1074/jbc.RA118.006561]