My research has focussed upon protein biogenesis within a group of positive-stranded RNA viruses, the Picornaviruses. Such viruses possess a single, long, open reading frame, but must generate multiple proteins for their RNA replication and encapsidation: they encode a 'polyprotein'. My work at the IAH, Pirbright on Foot-and-Mouth Disease virus (FMDV) indicated that one polyprotein 'cleavage' event was most unusual. This work was carried forward and expanded at St Andrews where we determined that this 'cleavage' event was not proteolytic, but was a novel translational 'recoding' event mediated by an oligopeptide sequence: '2A'. Our present work involves the molecular mechanism of this recoding event, the use of this system for biomedical and biotechnological applications and the occurrence of '2A-like sequences in other viral and cellular sequences.

   Relatively recently, permission was granted by HSE/DEFRA for St Andrews to work with the FMDV 'replicon' - stimulating a major new line of research. In collaboration with the Pibright Institute and the Universities of Leeds, Dundee and Edinburgh (initially funded by the Wellcome Trust, but now funded by a BBSRC SLoLa grant), the consortium has embarked upon a comprehensive study of the molecular biology of FMDV replication. A substantial component of this program of work involves harnessing modern molecular approaches for the development of a new generation of FMDV vaccines.

Picornaviruses, polyprotein processing, virus-encoded proteinases, Foot-and-Mouth Disease Virus, Vaccine development.

Future work on 2A encompasses (i) the continued development of 2A for biomedical/biotechnological applications, (ii) determining the activties and functions of cellular 2A-like sequences, and (iii) the replication of FMDV using the 'replicon' system. Future work using the FMDV replicon involves (i) fundamental studies on FMDV RNA replication and (ii) the development of new FMDV vaccines.

We have developed techniques for co-ordination of protein expression using self-processing polyproteins. This strategy has the advantage that multiple products can be generated from a single transcription unit. This has lead to major advances in gene therapy, biomedicine (notably the generation of induced human pluripotent stem cells; iPSCs) and biotechnology - both animal and plant.

We have created a panel of (replication) attenuated FMDV genomes. Corresponding, infectious, viruses are being 'rescued' at the Pirbright Institute. This program of work has huge potential for increasing the security of food supplies and generating new products - live, attenuated, FMDV vaccines.

Ph.D., Molecular Virology, University of Leicester;

M.Sc., Microbiology, University of London, Birkbeck College;

B.Sc., Plant Biochemistry, University of London, King's College