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Elucidating the structure of previously inaccessible fusion intermediates of Influenza A Virus by cryo-electron microscopy

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  • Full or part time
    Dr Juan Fontana
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

A PhD position is available in the laboratory of Juan Fontana (University of Leeds; http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=JF).

Influenza virus infects 5-10% of adults yearly. Furthermore, the emergence of novel strains can result in a pandemic flu. To start an infection, Influenza has to release its genetic material inside the target cell. This process requires the merging (fusion) of the viral and cellular membranes, which is mediated by a single viral surface protein, hemagglutinin. This critical protein transits from an initial relatively unstable conformation, to a final more stable conformation. However, the intermediate conformations of this process are poorly understood. Elucidating the structure of these intermediates will reveal new antiviral targets to hinder Influenza infection.

Cutting-edge electron microscopy techniques, which allow visualisation of viruses at the atomic or molecular level, will be employed by the student to increase the understanding of Influenza fusion. First, fusion will be imaged under laboratory-controlled conditions, studying isolated fusion proteins and/or virus-like particles interacting with artificial membranes. These experiments will generate high-resolution structures of the intermediates. The student will also characterise how Influenza virus fuses with its cellular target membranes, which has been traditionally limited since cells are too large to be imaged by electron microscopy. These results will allow the student to correlate the findings from the laboratory-controlled conditions with fusion inside cells, confirming that the proposed targets for blocking Influenza fusion also exist in biologically-relevant conditions.

Talented and motivated students passionate about research are invited to apply for this PhD position. The successful applicant will join the Faculty of Biological Sciences Post-Graduate Research Program at the University of Leeds, which has been named University of the Year 2017 by The Times and The Sunday Times’ Good University Guide. The student will also join the Astbury Centre for Structural and Molecular Biology, which has recently invested ~£10M in a new cryo-electron microscopy facility, making it competitive with the best in the world.

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject. They should also have appropriate research experience and/or a Masters degree in a relevant subject. Experience in either virology and cell culture; or in electron microscopy imaging and data processing is required. Training can be provided in cryo-electron microscopy, tomography, cell culture, manipulation of viruses in bio-safety level 2, fluorescence and confocal microscopy, among other techniques.

Further details are available from Dr. Juan Fontana ([email protected]).

Funding Notes

The position is funded for three years by a Springboard Award from the Academy of Medical Sciences (which is supported by the Wellcome Trust) and the University of Leeds.

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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