Lead supervisor: Dr Chris H Hill
Co-supervisors: Dr Christoph Baumann, Dr Trevor Sweeney (The Pirbright Institute) and Dr Steven Quinn
The student will be registered with the Department of Biology
Enteroviruses (e.g. poliovirus, enterovirus 71, rhinovirus) comprise a diverse group of human and animal pathogens, which together are estimated to cause over one billion infections annually. Once inside the host cell, their positive-sense, single-stranded RNA genomes must be replicated by first synthesizing a negative-sense strand followed by a new positive-sense RNA molecule. The primer for RNA synthesis is the uridylated form of VPg, a small viral protein.
The enterovirus genome is highly structured, and several conserved RNA structures are essential regulators of genome synthesis. A “cloverleaf” structure at the 5′ end of RNA binds to both host poly(rC)-binding protein 2 (PCBP2) and the viral 3CD protein – a precursor form of the mature 3C (protease) and 3D (polymerase) proteins. The cis-replicative element “cre”, required for VPg uridylation by 3D, binds to both 3CD and 3C proteins. However, our understanding of this network of interactions has been hampered by the lack of high-resolution three-dimensional structures.
You will study the structural and mechanistic basis of cloverleaf/PCBP2/3CD and cre/3C/3CD complex assembly. This will involve the reconstitution of RNA-protein complexes in vitro, purification of complexes, sample optimization, cryo-EM data collection and processing. You will also study protein-protein and protein-RNA-interactions using a variety of single-molecule biophysical techniques to probe RNA conformational dynamics and the kinetics of complex assembly. Key findings will be further explored in virus-infected cells, in collaboration with the Sweeney group (Pirbright Institute). You will join an interdisciplinary, diverse and highly supportive training environment with the combined expertise of four supervisors: structural biology and RNA biochemistry (Hill group), advanced single-molecule imaging (Baumann and Quinn groups) and enterovirus molecular biology (Sweeney group). You will also benefit from access to state-of the art cryo-EM infrastructure at YSBL, and the Molecular Interactions laboratory in the Bioscience Technology Facility. Candidates from under-represented groups are particularly encouraged to apply.
The Departments of Biology and Chemistry both hold an Athena SWAN Gold Award. We are committed to supporting equality and diversity and strive to provide a positive working environment for all staff and students.
The WR DTP and the University of York are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with any biological, chemical, and/or physical science backgrounds, or students with mathematical background who are interested in using their skills in addressing biological questions.
Programme: PhD in Mechanistic Biology (4 years)
Start Date: 16th September 2024
Shortlisted candidates will be interviewed by the WR DTP panel in February 2024 on a date to be confirmed.