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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

Mazzon M, et al (2018). Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic changes. PLoS pathogens, 14 (1), e1006835. doi:10.1371/journal.ppat.1006835
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
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
The National Institutes of Health
 

Research Themes

Virus entry, Membrane trafficking, Cellular mechanisms of viral restriction, Viral pathogenesis

Technology

Light microscopy, Translational research, Bioinformatics, Electron microscopy

People

Michela Mazzon (Postdoctoral Research Associate)
Scott Lawrence (Postdoctoral Research Associate)
Kristin Vassileva (PhD student, joint with Sandi Patel, CDB, UCL)
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)