About the Project
Patients with kidney transplants can develop a number of complications that result in the failure of the transplant. One of these is caused by infection with the BK polyomavirus (BKV). BKV causes a severe disease called polyomavirus-associated nephropathy (PVAN), which afflicts up to 10% of all kidney transplant patients. There are no effective therapies for this disease and we currently have a poor understanding of the virus life cycle. This studentship will utilize a combination of molecular, cellular and virological assays, established in the group, to study both host and virus factors that contribute to BKV infection and pathogenesis. Using primary cell culture model systems we will study the specific roles of BKV proteins during infection, with a particular emphasis on the enigmatic agnoprotein. Mutant viruses will be created and their abilities to infect will be tested. In addition, using a novel lentiviral library system, we will screen for host proteins implicated in virus infection. Together, these studies will increase our understanding of the BKV life cycle and may identify targets for therapeutic intervention.
Funding Notes
The PhD will start in Oct 2016. Applicants should have, or be expecting to receive, a 2.1 Hons degree in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support.
References
Hurdiss DL, Morgan EL, Thompson RF, Prescott EL, Panou MM, Macdonald A, Ranson NA. (2016). New Structural Insights into the Genome and Minor Capsid Proteins of BK Polyomavirus using Cryo-Electron Microscopy. Structure. 2016 Apr 5;24(4):528-36
Richards, Watherston, Doble, Blair, Wittmann & Macdonald (2015). Human papillomavirus (HPV) E7 protein antagonises a novel imiquimod-induced inflammatory pathway in primary keratinocytes. Scientific Reports. 13;5:12922.
Muller, Wasson, Bhatia, Boxall, Millan, Goh, Haas, Stonehouse & Macdonald (2015). YIP1 family member 4 (YIPF4) is a novel cellular binding partner of the papillomavirus E5 proteins. Scientific Reports. 3;5:12523.
Hughes, D.J., Wood, J.J., Jackson, B.R., Baquero-Perez, B. & Whitehouse, A. (2015). NEDDylation is essential for Kaposi's sarcoma-associated herpesvirus latency and lytic reactivation and represents a novel anti-KSHV target. PLoS Pathogens, 11(3):e1004771.
Jackson, B.R., Norenberg, M. & Whitehouse, A. (2014). A novel mechanism inducing genomic instability in Kaposi’s sarcoma-associated herpesvirus infected cells. PLoS Pathogens, 10(5): e1004098.
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