Probing the Function of RNA Structural Elements in the FMDV Genome using Biophysical and Genetic Approaches

This studentship is open to science graduates with, or who anticipate obtaining, at least a 2:1 or equivalent in a relevant biological subject in an undergraduate degree, or with a Masters degree – subject to university regulations. Other first degrees, e.g. veterinary science, will be considered. You should be looking for a challenging, interdisciplinary research training environment and have an active interest in the control of infectious diseases.

Students without English as a first language must provide evidence that they meet the English language requirement, e.g. with an average IELTS score of 7.0, with no lower than 7.0 in listening/reading and no lower than 6.5 in speaking/writing.

Foot-and-mouth disease is a highly contagious disease of cattle, sheep and pigs that causes huge economic loss in some of the poorest countries in the world and threatening food security. Outbreaks in the UK have previously led to mass culling and damaged national and international trade. The disease is caused by the foot-and-mouth disease virus (FMDV), a small single stranded RNA virus. The FMDV RNA genome is highly structured with different structural elements being important for different stages of the viral lifecycle.

We have previously shown that RNA structures, called pseudoknots, in the non-coding region at the 5’ end of the genome are important for packaging viral RNA into new virus particles, a key stage in generating new viruses. A separate RNA structure termed the cis-replicative element (cre) acts as a template for VPg uridylation, essential for viral genome synthesis. As both these processes are restricted to viral replication they present novel targets for the development of novel, specific anti-viral approaches. However, we currently lack a detailed mechanistic understanding of how these processes work.

You will study the structural and mechanistic basis of dynamic pseudoknot formation and cre-directed VPg uridylation. This will involve the reconstitution of RNA-protein complexes in vitro, purification of complexes, biochemical assays to study VPg uridylation, sample optimization, X-ray crystallography and cryo-EM data collection and processing. You will also study protein-protein and protein-RNA-interactions using a variety of single-molecule imaging techniques (e.g. TIRF, FRET) to probe RNA conformational dynamics and the kinetics of complex assembly. Key findings will be further explored using FMDV reverse genetic approaches in virus-infected cells. No previous experience in these techniques is necessary and you will receive a thorough experimental training. Candidates from under-represented groups are particularly encouraged to apply.

You will join a vibrant, diverse and highly supportive training environment with the combined expertise of different supervisors with already well-established collaborative projects. You will benefit from rapid and frequent access to state-of the art X-ray crystallography and cryo-EM infrastructure at the York Structural Biology Laboratory (https://www.york.ac.uk/chemistry/research/ysbl/facilities/eleanor-and-guy-dodson-building), and unique high containment facilities at The Pirbright Institute. 

The successful student will be registered with the University of York and spend a period of their PhD training at the University of York and The Pirbright Institute. The student will visit both locations to meet with their supervisors and undertake training or complete specific project tasks as required.

TO APPLY: Full details of how to apply please visit our website: Postgraduate studentships nearmejobs.eu The Pirbright Institute

For informal enquiries regarding this project please contact the project supervisors. For enquiries regarding eligibility and the application process please email studentship@pirbright.ac.uk