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Immunity to Influenza and Ebola viruses

  • Full or part time
  • Application Deadline
    Friday, January 10, 2020
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

This started with the investigation of T cell recognition of peptides derived from intracellular proteins of Influenza (Townsend et al 1986), that evolved into the development of a live attenuated, single cycle Influenza vaccine, based on these principles (Powell et al, 2012; Baz et al, 2015, Holzer 2018). In recent years we have extended our interest to the protective antibody response analysed by cloning human B cells. In particular the role of highly focused B cell responses to haemagglutinin in driving the evolution of seasonal influenza (Huang et al 2015), broadly protective antibodies to the Neuraminidase (Rijal et al 2019) and the breadth and function of antibody responses to avian influenza viruses that are pandemic threats (Huang et al 2019).

Following the epidemic of Ebola in West Africa in 2014 we extended our interest to the immune response to Ebola virus. From a biological viewpoint Ebola and Influenza are related in having an RNA genome, containing a lipid envelope, and a trimeric Glycoprotein that acts as both receptor and fusion protein. In partnership with the antibody discovery unit of the company UCB (Slough, UK) and Simon Draper’s group at the Jenner Institute (Oxford) have examined the repertoire of antibodies induced in volunteers immunised with an experimental Ebola vaccine, and selected out a therapeutic cocktail (Rijal et al 2019). We are continuing to investigate how protective antibodies function through an international collaboration with the Viral Immunotherapeutics Consortium (Saphire et al 2018). We have also developed our own Ebola surrogate that has been useful for screening a small drug library for inhibitors of Ebola entry into cells (Xiao et al 2018). This has led to an extended collaboration with the Department of Pharmacology in Oxford to analyse the mechanism of action of these drugs.

These projects involve a very wide range of techniques, offer a broad spectrum of interests from which to select projects for a D.Phil., and provide many opportunities for collaborative work.

Additional supervision may be provided by Dr Pramila Rijal and Dr Tiong Tang.

Our interests are broad, and our philosophy is that whatever technique is required to answer a particular question we can teach it if it is part of our local armoury, or will find a laboratory in Oxford or beyond that has mastered it and can transfer the needed skills. The environment in the WIMM and in the University is highly collaborative and we all take part in a continual exchange of knowledge and skills.

Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division’s Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

All WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework. The RDM also holds an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Funding Notes

Funding for this project is available to scientists through the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.
For October 2020 entry, the application deadline is 10th January 2020 at 12 noon (midday).
Please visit our website for more information on how to apply.

References

Rijal P, Elias SC, Machado SR, Xiao J, Schimanski L, O'Dowd V, Baker T, Barry E, Mendelsohn SC, Cherry CJ, Jin J, Labbe GM, Donnellan FR, Rampling T, Dowall S, Rayner E, Findlay-Wilson S, Carroll M, Guo J, Xu XN, Huang KA, Takada A, Burgess G, McMillan D, Popplewell A, Lightwood DJ, Draper SJ, Townsend AR. 2019. Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans. Cell Rep

Rijal P, Wang B, Tan TK, Schimanski L, Janesch P, Dong T, McCauley JW, Daniels RS, Townsend AR, Huang KA. 2019. Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans. bioRxiv

Xiao JH, Rijal P, Schimanski L, Tharkeshwar AK, Wright E, Annaert W, Townsend A. 2018. Characterization of Influenza Virus Pseudotyped with Ebolavirus Glycoprotein. J Virol

Huang KY, Rijal P, Schimanski L, Powell TJ, Lin TY, McCauley JW, Daniels RS, Townsend AR. 2015. Focused antibody response to influenza linked to antigenic drift. J Clin Invest

Huang KA, Rijal P, Jiang H, Wang B, Schimanski L, Dong T, Liu YM, Chang P, Iqbal M, Wang MC, Chen Z, Song R, Huang CC, Yang JH, Qi J, Lin TY, Li A, Powell TJ, Jan JT, Ma C, Gao GF, Shi Y, Townsend AR. 2018. Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans. Nat Microbiol

Morgan SB, Hemmink JD, Porter E, Harley R, Shelton H, Aramouni M, et al. 2016. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus. J Immunol

Baz M, Boonnak K, Paskel M, Santos C, Powell T, Townsend A, et al. 2015. Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge. MBio

Powell TJ, Silk JD, Sharps J, Fodor E, Townsend AR. 2012. Pseudotyped influenza A virus as a vaccine for the induction of heterotypic immunity. J Virol

Powell TJ, Rijal P, McEwen-Smith RM, Byun H, Hardwick M, Schimanski LM, Huang KA, Daniels RS, Townsend ARM. 2019. A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins and protection from heterotypic challenge. J Gen Virol


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FTE Category A staff submitted: 238.51

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