Virus remodelling of host-cell endomembranes (360G-Wellcome-098406_Z_12_B)

£599,947

Enveloped viruses appropriate host-cell membranes to assemble their progeny. Large DNA viruses achieve this by dramatically remodelling the host-cell endomembrane system. I work at the intersection of virology and membrane trafficking, exploiting the intimate connection between viruses and their host cells to gain insights into both virus biology and the dynamic regulation of cellular membranes. I will combine biophysics, biochemistry and cell-based infection assays to investigate the conserved mechanisms by which human herpesviruses change the composition and architecture of intracellular membranes, addressing two questions: What is the role of ceramide transport in the biology of enveloped viruses? We have identified a direct interaction between a conserved herpesvirus protein and a cellular ceramide transporter. This suggests that herpesviruses actively modify the ceramide composition of intracellular membranes during infection, a new paradigm in virus:host interactions. How do enveloped viruses bend membranes during assembly? We have identified a conserved protein complex that promotes herpesvirus membrane wrapping, potentially via palmitoylation-dependent sensing and/or stimulation of membrane curvature. A detailed molecular understanding of how viruses subvert host-cell membranes not only expands our knowledge of host and virus biology, but it provides the basic underpinning science for the next generation of vaccines and antiviral therapies.

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Grant Details

Amount Awarded 599947
Applicant Surname Graham
Approval Committee Sir Henry Dale Fellowship Interview Committee
Award Date 2017-10-18T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Sir Henry Dale Fellowship Extension
Internal ID 098406/Z/12/B
Lead Applicant Dr Stephen Graham
Partnership Name Royal Society/Wellcome Trust Sir Henry Dale Fellowship
Partnership Value 599947
Planned Dates: End Date 2021-02-01T00:00:00+00:00
Planned Dates: Start Date 2018-02-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Geoffrey Smith