Research Fellow in Structural Molecular Virology

Project Title: The roles of the pre-genomic RNA in Hepatitis B Virus nucleocapsid assembly

This project aims to determine the detailed molecular mechanism used by Hepatitis B Virus (HBV) in assembling its nucleocapsid using a combination of structure determination (especially electron microscopy), biophysics and biochemistry. HBV is estimated to have infected more than 2 billion people across the world, where chronically infected carriers can be >10% of the local population. Such carriers often progress to liver cancer or cirrhosis resulting in hundreds of thousands of deaths per annum. Current therapeutic options are very limited, so new drug targets such as those we will investigate during this project are urgently required.

This post offers an opportunity to join a highly productive, interdisciplinary team headed by Professor Peter Stockley (Leeds, where the post will be based) and Professor Reidun Twarock (York). Our team spans a wide range of expertises, including evolutionary biology and mathematical modelling (Twarock), structural virology (Neil Ranson, Joe Cockburn, Juan Fontana & David Rowlands), molecular genetics & biochemistry (Stockley), and biophysics (Roman Tuma).  Our wider goal is to understand the molecular mechanisms used by ssRNA viruses to assemble their capsids during an infection cycle, and the constraints that these mechanisms place on their evolution. Such insights will enable the development of future anti-viral strategies. This class of viruses is ubiquitous in all kingdoms of life, causing devastating diseases in humans, animals and crop plants. They also constitute a significant fraction of newly emerging viral infections, so new therapeutic/defensive strategies are urgently required. HBV is part of this analysis because it initially assembles a nucleocapsid around a pre-genomic ssRNA version of its genome that is converted to DNA once encapsidated. Our hypothesis is that increased understanding of fundamental mechanisms will identify novel anti-viral targets.

We are looking for an ambitious, highly motivated structural biologist.

• You should have a PhD in structural biology or electron microscopy, although a motivated X-ray crystallographer with a desire to cross-train into EM will also be considered.
• Previous experience in one or more of the following areas is essential; microbiology, virology, biochemistry/chemistry, molecular genetics, or a closely allied discipline, including fluorescence spectroscopy, as will a strong drive to learn new techniques and tackle complex macromolecular systems.
• Your work will be at the interface between structural biology and Biochemistry/Biophysics.
• You will work on a day-to-day basis under the supervision of the grant PI, and actively collaborate with a large interdisciplinary team across the Stockley/Twarock research groups.
• In addition, you will be expected to develop and implement new methods and participate in the supervision of graduate students.

Stockley & Twarock are Wellcome Trust Joint Investigators, so extension of the post beyond the initial two-year period is a possibility.

Informal enquiries may be made to Professor P. G. Stockley, email p.g.stockley@leeds.ac.uk or Dr. N. A. Ranson, email n.a.ranson@leeds.ac.uk

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