About the Project
Emerging and re-emerging viruses such as influenza, Zika, Ebola, and Dengue continue to be a large threat to human health. The recent outbreaks of Zika in the Americas, Ebola in West Africa, and avian influenza across the world signifies the socio-economic impact of emerging viral disease. Of those, influenza is an important zoonotic virus that causes outbreaks in poultry, wild birds, swine, and other mammals. Five hundred million humans are infected with influenza each year, of which about 500,000 cases lead to death. Universal vaccines for influenza are lacking, and in order to develop novel cellular antivirals a comprehensive understanding of the cell biology of virus infection and virus-host interactions is necessary.
Influenza A virus (IAV) is an enveloped virus that belongs to the Orthomyxoviridae with high economic, social, and medical relevance. Viruses are intimately connected and dependent on their host for propagation. In many cases this relationship leads to severe disease in humans. Uncoating is a key process for viruses during entry and infection [1-2]. The IAV entry process requires host factors that unpacks the infectious genome from the protective capsid and viral envelope [3-4]. The PhD project will focus on ubiquitin-regulated aspects (and others that are not shown here, upon discussion and within the capacity of the candidate) and cellular factors that regulate IAV entry and uncoating [4-6].
Candidates who have prior experience with cell biology, biochemistry, cloning, confocal fluorescence microscopy, live/fixed-imaging, etc. are encouraged to apply. Prior experience in virology is not necessary. We value out-of-the-box and critical thinking, team work, passion for experiments and self-motivation to solve scientific questions. Mechanistic studies will be performed using biochemistry, cell biology, molecular biology, microscopy (high content imaging [7], fluorescence light/EM), virus entry/infection/replication assays, small-mid scale siRNA screening, CRISPR/Cas9 genome editing, FACS, viral reverse genetics, proteomics, super resolution microscopy (within the expertise of our lab and in house collaborators), structural biology and microfluidics (in house and international collaborations). The PI is a co-affiliate of a Swiss SystemsX.ch MRD program (VirX) until end of 2018, and the candidate will have opportunities to interact with the consortium during the first year of their PhD.
Directly apply online at http://www.bristol.ac.uk/study/postgraduate/apply/
You should select ’Faculty of Biomedical Sciences’ and then ’Cellular and Molecular Medicine (PhD)’
Yamauchi Lab website: http://www.yamauchilab.com/
Funding Notes
This is a fully-funded 3 year studentship open to UK students and eligible EU students who qualify for home-rated fees. Eligible students will receive a minimum annual stipend of £14,553 and university registration fees will be paid.
Open to science graduates (with, or who anticipate obtaining, at least 2.1 or equivalent in relevant biological subject in undergraduate degree, or a Masters degree). Other first degrees, e.g. veterinary science, considered. A good command of both written and spoken English is required.
References
[1] Helenius A. Unpacking the incoming influenza virus. Cell 1992 May 15;69(4):577-8.
[2] Yamauchi Y, Greber UF. Principles of Virus Uncoating: Cues and the Snooker Ball. Traffic. 2016 Jun;17(6):569-92.
[3] Edinger T. et al., Entry of influenza A virus: host factors and antiviral targets. J Gen Virol. 2014 Feb;95(Pt 2):263-77.
[4] Rudnicka A, Yamauchi Y. Ubiquitin in Influenza Virus Entry and Innate Immunity. Viruses. 2016 Oct 24;8(10).
http://www.mdpi.com/1999-4915/8/10/293
[5] Banerjee I. et al., Influenza A virus uses the aggresome processing machinery for host cell entry. Science. 2014 Oct 24;346(6208):473-7.
http://scienceintheclassroom.org/research-papers/mimicking-bundle-waste-influenza-virus-strategic-attack/university
[6] Stauffer S. et al., Stepwise priming by acidic pH and a high K+ concentration is required for efficient uncoating of influenza A virus cores after penetration. J Virol. 2014 Nov;88(22):13029-46.
[7] Banerjee I. et al., High-content analysis of sequential events during the early phase of influenza A virus infection. PLoS One. 2013 Jul 12;8(7):e68450.
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