Coordinated use of the hepatitis C virus genome during the virus lifecycle. (360G-Wellcome-096670_Z_11_Z)

£1,610,588

My vision is to achieve a comprehensive understanding of key events in the hepatitis C virus (HCV) lifecycle, with the ultimate goal of developing new antivirals. The research questions that underpin this vision are to define in molecular detail the processes by which the virus genome is replicated and packaged into virus particles, and determine how these events are coordinated.Specifically, I propose to exploit a combination of cell biological, biochemical and biophysical approaches, to address the following major overarching and unanswered questions: 1) What is the structure and compositionof the macromolecular complex that replicates the genome? 2) How is the viral genome packaged into nascent particles? 3) What are the mechanisms that allow the genomic RNA to be selected for either of these two processes? Addressing these questions is fundamentally important in the future development of much needed new therapies for the treatment of HCV, a pathogen which leads to long-term liver disease with a poor prognosis, infecting 3% of the global population with a further 3-4 million new cases each year. Despite the advent of candidate direct-acting antivirals targeted to HCV, treatment options for patients remain limited, in stark contrast to the situation for patients infected with HIV. Driven by remarkable progress in molecular understanding ofHIV biology, 30 different compounds are available for treatment of HIV infection; these have six distinct well-characterised modes of action and effectively control disease. The challenge is to provide HCV patients with similar therapeutic opportunities, the lesson from HIV is that this can only be achieved if underpinned by a comprehensive molecular understanding of virusbiology. Attaining this goal is at the heart of my research vision, by offering new insights into the HCV lifecycle and providing a solid platform for the development of novel chemotherapeutics, it also maps directly on to the Wellcome Trusts major challenge of combating infectious disease.

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Grant Details

Amount Awarded 1610588
Applicant Surname Harris
Approval Committee Science Interview Panel
Award Date 2011-10-04T00:00:00+00:00
Financial Year 2011/12
Grant Programme: Title Investigator Award in Science
Internal ID 096670/Z/11/Z
Lead Applicant Prof Mark Harris
Partnership Value 1610588
Planned Dates: End Date 2018-06-12T00:00:00+00:00
Planned Dates: Start Date 2012-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber