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  Structural studies of Pestiviruses envelope glycoproteins


   BBSRC Interdisciplinary Bioscience DTP

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  Dr K El Omari  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

Pestiviruses are a family of viruses with significant economic impact on animal production worldwide. The most notable pestiviruses are bovine viral diarrhea virus (BVDV), classical swine fever virus (CSFV), and border disease virus (BDV), infecting cattle, pigs, and sheep, respectively. Pestiviruses are responsible for clinical symptoms ranging from respiratory disorders to abortions.

Efforts are being made to detect outbreaks at early stages to prevent disasters such as that which occurred in the Netherlands in 1997 where 11 million pigs were killed to prevent the virus from spreading. Pestiviruses are positive-sense single-stranded RNA enveloped viruses. Their genome encodes a single polyprotein, which is cleaved by viral and cellular proteases into structural and non-structural proteins. Of the three structural glycoproteins (Erns, E1, and E2) located on the outer surface of the virion, E1 and E2 form heterodimers and are responsible for cell attachment and membrane fusion.

The mechanism of viral fusion of pestiviruses has not yet been determined, so this project focus on unravelling this mechanism by structural studies of the envelope fusion glycoproteins E1 and E2 and the heterodimer E1:E2 from different pestiviruses (BVDV, CSFV and BDV), as well as their cellular receptors. During this PhD project, the student will express and purify the different proteins of interest from mammalian expression systems in order to either carry out protein crystallization or produce grids for electron microscopy. The students will have access to state of the art facilities at the Diamond Light Source and the Division of Structural biology to undertake crystallographic or electron microscopy studies.

Understanding viral attachment and/or viral fusion would help to block viral infection; therefore pestiviruses E1 and E2 glycoproteins are very attractive targets for drug therapy. In addition, an empty viral shell (without the genome) harbouring on the surface, E1 and E2, could also be used as a potential vaccine since these proteins are immunogenic. Finally, E1 and E2 glycoproteins could also be used for the production of therapeutic antibodies.

To apply: http://www.biodtp.ox.ac.uk/how-to-apply/index.html

Funding Notes

This project is funded for four years by the Biotechnology and Biological Sciences Research Council BBSRC and Diamond Light Source. BBSRC eligibility criteria for studentship funding applies (http://www.bbsrc.ac.uk/documents/studentship-eligibility-pdf/). Successful students will receive a stipend of £16,300 per annum.