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LMCB - MRC Laboratory for Molecular Cell Biology

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Mark Marsh's picture
LMCB Director, LMCB Group Leader
 
+44 (0)20 7679 7807
LMCB Room 1.14
 
 
 
Cellular Mechanisms of Virus Entry and Assembly

Research Synopsis

The mechanisms used by viruses to invade and replicate in cells are of fundamental interest, both in terms of improved understanding of infection and pathogenesis, with implications for health and economic wellbeing, but also because viruses are extraordinary tools for revealing how cells work. We focus on understanding how membrane-containing enveloped viruses interact with cellular membrane systems, how these interactions facilitate or restrict the transmission of viruses from cell to cell and how they impact on viral pathogenesis. We are exploiting our current knowhow to develop knowledge-based interventions against viral infections and/or pathogenesis. Recently, we have concentrated on HIV, and the closely related simian immunodeficiency viruses (SIV), with a view to understanding fundamental aspects of virus replication in macrophages and how highly conserved trafficking signals in the envelope glycoprotein of SIV impact on pathogenesis. In new programs of work, we will investigate (1) how interferon-induced transmembrane (IFITM) proteins inhibit the entry of a broad range of enveloped viruses, (2) the potential to develop broad-spectrum antivirals that inhibit the entry of viruses that exploit the same endocytic entry mechanisms, and (3) the cell biological processes underlying virus particle formation. 

Selected Publications

Weston S, et al (2016). Alphavirus restriction by IFITM proteins. Traffic (Copenhagen, Denmark).
Nkwe DO, et al (2016). The intracellular plasma membrane-connected compartment in the assembly of HIV-1 in human macrophages. BMC Biology, 14 (1). doi:10.1186/s12915-016-0272-3
Grove J, et al (2014). Flat clathrin lattices: stable features of the plasma membrane. Mol Biol Cell, 25 (22), 3581-3594. doi:10.1091/mbc.E14-06-1154
Weston S, et al (2014). A membrane topology model for human interferon inducible transmembrane protein 1. PLoS One, 9 (8), e104341-?. doi:10.1371/journal.pone.0104341
Vermeire K, et al (2014). Signal peptide-binding drug as a selective inhibitor of co-translational protein translocation. PLoS Biol, 12 (12), e1002011-?. doi:10.1371/journal.pbio.1002011
Giese S & Marsh M (2014). Tetherin can restrict cell-free and cell-cell transmission of HIV from primary macrophages to T cells. PLoS Pathog, 10 (7), e1004189-?. doi:10.1371/journal.ppat.1004189

Funders

Medical Research Council
UCL Confidence in Concept

Research Themes

Cytoskeleton and cell cortex, Polarity and cell shape, Cell-cell interactions, Membrane trafficking, Viral pathogens

Technology

Light microscopy, Translational research, Bioinformatics, Electron Microscopy

People

Michela Mazzon (Postdoctoral Research Associate)
Scott Lawrence (Postdoctoral Research Associate)
Caron Jacobs (PhD student, joint with Ricardo Henriques, MRC LMCB)
Farrell Mackenzie (Research Assistant)
 

Collaborators

Ricardo Henriques (LMCB, UK)
Jason Mercer (LMCB, UK)
Ewa Paluch (LMCB, UK)
Dan Cutler (LMCB, UK)
Franck Pichaud (LMCB, UK)
Chris Stefan (LMCB, UK)
Robin Ketteler (LMCB, UK)
Jim Hoxie (University of Pennsylvania, USA)
Mark von Zastrow (UCSF, USA)
Andrew Shevchuk (Imperial College, UK)
Greg Towers (UCL, UK)
Isabel Llorente-Garcia (UCL, UK)
Paul Kellam (Imperial College, UK)
Mike Jacobs (UCL, UK)
Richard Angel (UCL, UK)
Sandip Patel (UCL, UK)