About the Project
Human cytomegalovirus (HCMV), is a common global pathogen, the dominant viral cause of congenital birth defects in the developed world and a rising vaccine priority. HCMV is also a major viral opportunistic infection in HIV/AIDS increasing morbidity and mortality. This is one of the largest DNA viruses, presenting challenges in understanding the remarkable complexity in its entry machinery as compared to smaller enveloped viruses (e.g. HIV or Influenza). A structural view of the entry process, will be a critical step in identifying potential novel therapeutics, including vaccines and drugs.
The aim of this PhD is to build a structural model of the core HCMV fusion machinery during cellular infection by developing a mathematical/computational modelling approach that will combine data from natural transmission pathways, cryoET (in collaboration with Professor Kay Grünewald’s lab, University of Oxford), X-ray crystallography, genomics and genotypic variation. Using this integrated approach the project aims to identify molecular mechanisms underlying HCMV entry stage into the host cell and therapeutic targets.
Funding Notes
The successful applicant will begin their PhD studies in September 2016 with a tax-free stipend of over £1,300 per month and tuition fees paid in full at the home/EU rate.
The maximum duration of this studentship is 3 years.
References
[1] Gompels UA, Larke N, Sanz-Ramos M, Bates M, Musonda K, Manno D, Siame J, Monze, M, Filteau S; CIGNIS Study Group. (2012) Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia. Clin Infect Dis. 54:434-42.
[2] Maurer UE, Zeev-Ben-Mordehai T, Pandurangan AP, Cairns TM, Hannah BP, Whitbeck JC, Eisenberg RJ, Cohen GH, Topf M, Huiskonen JT, Grünewald K. (2013). The structure of herpesvirus fusion glycoprotein B-bilayer complex reveals the protein-membrane and lateral protein-protein interaction. Structure 21:1-10.
[3] Bates M, Monze M, Bima H, Kapambwe M, Kasolo FC, Gompels UA, CIGNIS group. (2008) High human cytomegalovirus loads and diverse linked variable genotypes in both HIV-1 infected and exposed, but uninfected, children in Africa, Virology 382:28-36.
[4] Pandurangan AP, Vasishtan D, Alber F, Topf M (2015) γ-TEMPy: simultaneous fitting of components in 3D-EM maps of their assembly using a genetic algorithm. Structure 23:2365-76
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