Jonathan Grimes

Jonathan
Grimes

University of Oxford
Biography

I am a Nuffield Department of Medicine Senior Research Fellow, and an Associate Professor in the Division of Structural of Biology (STRUBI), as well as holding a DIAMOND Research Fellowship. I completed my BSc (Hons.) Biochemistry at Bristol University, before receiving a DPhil from the University of Oxford.  This was followed by postdoctoral training at the University of Oxford and EMBL Grenoble, where I also worked at the European Synchrotron Radiation Facility (ESRF).  In 1999 I was recruited back to Oxford, and was awarded a Royal Society Research Fellowship which allowed me to establish my research group, where we employ structural biology, biochemical and cellular methods to study viruses.  I have over 20 years of extensive experience in structural virology and particularly in the structure determination of large macromolecular complexes. Examples include the structure of the Bluetongue virus core (BTV) particle, a tour-de-force for crystallography at the time, as well as the first crystal structure of a membrane-containing virus, phage PRD1. The work on BTV showed how 120 capsid proteins could be arranged on an icosahedral lattice, which at the time was “disallowed” under the accepted conceptual frameworks. The structure of PRD1 revealed the lipid bilayer, and the minor proteins that are involved in directing viral assembly. In addition I have contributed to the development of the ideas of using the structure of viral proteins and their architecture in the viral capsid, to understand the relationships and evolutionary links between seemingly different groups of viruses.

I determined the structure of the polymerase of bacteriophage Phi6, in complex with RNA and nucleotides, which provided the first model for the initiation of replication and transcription of an RNA virus. Very recently my group has solved the structures of components of the replication complexes of important human pathogens. We have solved the structure of the C-terminal portion of the L-polymerase of HMPV, the methyltransferase domain, which has a novel capping activity. In addition we have solved the structure of Influenza virus polymerase, which will be a start point to understanding how their genomes are replicated and how they switch to transcription.  I have recently been awarded a Wellcome Trust Investigator award to develop the work on Influenza virus replication and transcription to provide real biological insight into the mechanism of viral replication

Research interests

Structural Virology of Animal and Human Pathogens, and structural approaches to vaccines and therapeutics