Title of project: Role of autophagy in virus infection of mosquito cells Director of Studies: Dr P Fitzgerald Second Supervisor: Dr S Galbraith Overview of project Mosquito borne flaviviruses such yellow fever, West Nile (WN) and Dengue (DEN) are emerging due to the global spread of invasive mosquito species. Over 50% of the world is at risk from at least one flavivirus. In severe cases these viruses cause encephalitis, haemorrhagic fever and death. There are currently no vaccines available for DEN and WN control. Autophagy is a cellular response to starvation that provides a short term supply of amino acids by degrading proteins. Induction of autophagy in flavivirus infected mammalian cells inhibits virus growth. This proposal will determine the role of autophagy in flavivirus infection of mosquito cells, providing a mechanism to limit mosquito borne spread. Link to Faculty Research Themes School of Rehabilitation and Health Sciences, University of Glasgow Centre for Virus Research and University of Leeds. 3A (Allied Health Professions, Dentistry, Nursing and Pharmacy) and 5A (Biological Sciences). Outline of project including proposed timescales Induction of autophagy in mosquito cells limits the growth of intracellular bacteria (Wolbachia species) found in arthropods such as mosquitoes. Autophagy is known to inhibit the growth of another RNA virus (Rift Valley fever) in drosophila and mammalian cells. Nothing is known about the effect of autophagy on flavivirus infection of mosquito cells. This project will use Langat virus, a flavivirus not associated with human disease. Activation of autophagy in mosquito cells will be monitored by Atg8-II protein recruitment to autophagosomal membranes. Immunofluorescence microscopy will determine the role of autophagy in early events during Langat virus infection. Quantification of infectious virus by plaque assay will determine the effect of autophagy on Langat virus growth over time in the mosquito cells. This project will examine the role of autophagy in Langat virus infection of mosquito cells, which will be published in the Journal of Virology (impact factor 4.6). Knowledge about how autophagy is regulated during flavivirus infection of mosquito cells will provide insight into a novel mechanism to limit mosquito borne spread. This project will provide training in key virology, protein biochemistry and cell biology techniques. This will provide the student concerned with valuable skills for employment in academia or industry. Work arising from this proposal will be submitted as a program grant to the BBSRC to evaluate autophagy as a potential control mechanism for flavivirus infection of mosquitoes. Further information To apply you must be eligible for NHS Continuing Professional Development (CPD) funding and have the support of your line manager in writing. General enquiries should be directed by email to the Faculty Research Director r.hogston@leedsbeckett.ac.uk to discuss the project further please contact the Director of Studies P.Fitzgerald@leedsbeckett.ac.uk Applications should be made on line here http://www.leedsbeckett.ac.uk/research/research-degrees/research-studentships-andfees-only-bursaries/