Please address enquiries to Fred Antson. If you are contacting by email please attach an updated CV and explain your research and career interests.
- Details of postdoctoral and PhD research opportunities will be displayed here as they become available. There is currently 1 PhD position available (applications closing 11th January 2015), see below. PhD opportunities, including eligibility criteria, are also displayed on the University’s chemistry departmental website.
- The group is able to accommodate up to 2 undergraduate research students for summer vacation projects, usually for up to 10 weeks in the months July-September. Please tell us about any previous experience you have in your email.
- We are also able to accommodate students on research placements as part of their degree (e.g. through Erasmus), details of which should be discussed with Prof. Antson.
“Viral DNA-packaging motor nuclease: molecular snapshots along the reaction coordinate“
PhD in Biological Chemistry, White Rose Doctoral Training Partnership supported by BBSRC.
Professor Fred Antson (firstname.lastname@example.org) of the Department of Chemistry, and Professor Maggie Smith (email@example.com) of the Department of Biology.
Applications deadline: 11th January 2015. Interviews held: 4-5th February 2015.
Herpesviridae is a large family of human and animal viruses that are causative agents of a number of diseases ranging from common cold sores and chickenpox, to infectious mononucleosis and lymphoma. During virus particle assembly, herpes viruses and evolutionarily related tailed bacteriophages transfer their DNA into a protective protein capsid using a molecular motor. The large terminase protein is a key component of the viral motor, representing a viable target for drug development. Large terminase powers DNA translocation using its ATPase activity and cuts concatemeric DNA containing multiple sequential copies of viral genome into single copies, using its nuclease activity. It is unknown how this protein interacts with DNA and how its nuclease activity is switched on and off. It is known that nuclease activity can be inhibited by raltegravir, a potent inhibitor of the HIV integrase. However, it is completely unknown how this drug binds to herpes (and bacteriophage) nucleases.
This project will focus on understand the mechanism and regulation of the nuclease activity of the large terminase protein. A combination of biochemical, biophysical, and structural approaches will address the objectives: (a) define mutant proteins and chemical inhibitors that will enhance our mechanistic understanding and produce stable complexes of nuclease reaction intermediates; (b) characterize these complexes using biophysical, biochemical and high-resolution structural approaches; (c) use this information to conduct molecular modeling of the reaction mechanism and (d) to assay the consequences of point mutations and small molecule inhibitors in vivo. This iterative process will produce a library of high-resolution structural ‘snapshots’ of the reaction mechanism. This information will inform the development of novel approaches for fighting viral infections.