Quantitative proteomic analysis of the host-pandemic virus interaction
Evolution has produced an arms race between viruses and the cells they infect. Studying this battle provides key insights into cell biology and immunology, as well as the viruses themselves. It may even lead to the development of novel therapeutics. The Matheson lab therefore focuses on two pandemic viruses with a major impact on human health: HIV and SARS-CoV-2.
We have previously used unbiased proteomics to quantify dysregulation of hundreds of proteins and processes in infected cells, and now aim to understand the importance of these targets for both viral pathogenesis and normal cellular physiology. Because HIV regulates numerous cell surface amino acid transporters, we are particularly interested in amino acid metabolism and protein biosynthesis.
Depending on the interests of the student, this project will therefore focus on either (1) an orphan cell surface amino transporter downregulated by SARS-CoV-2 infection of respiratory epithelial cells or (2) an ancient metabolic enzyme regulating ribosomal frame shifting depleted by HIV infection of primary human CD4+ T cells.
In either case, the aims will be to: validate the target in different systems; define the mechanism of viral regulation; determine the functional effects of target depletion in biochemical and cell biological assays; and characterise the impact of target depletion on viral infection. Opportunities will be available to conduct further proteomic screens, perform ribosomal profiling and/or stable isotope-based metabolomics.
The project will provide training in a wide range of molecular and biochemical techniques, whilst allowing the student to explore an important aspect of the host-virus interaction. The Matheson lab is based in the brand new Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), including the largest academic Containment Level 3 (CL3) facility in the UK. The student will be supervised by an experienced postdoc in a friendly, supportive group.