logo
School of Veterinary Medicine and Science
   
   
  
 

James Leigh

Professor of Molecular Bacteriology; Head of Division of Animal Health & Welfare, Faculty of Medicine & Health Sciences

Contact

Biography

Professor Leigh has been investigating streptococci of significance to disease of livestock species since 1987. This work, originally conducted at IAH-Compton was relocated to University of Oxford in 2005 before finally arriving at the newly formed School of Veterinary Medicine & Science at the University of Nottingham in 2007. Professor Leigh's research interests range from investigation of bacterial epidemiology and the development / translation of molecular techniques for bacterial typing to investigation of host pathogen interactions involved in bacterial pathogenesis and studies on protein structure in relation to function. Professor Leigh's research has been strategically focussed at the control of disease by vaccination and other means and has over the years attracted considerable commercial collaboration. His present research exploits the availability of a completed genome, advancements in post genomic technologies (particularly proteomics), the ability to rapidly select mutants from an existing random mutant bank and the ability to utilise these in representative challenge models in the target species. The aim of these projects is to identify key components essential for virulence that may be used to develop effective vaccines

Expertise Summary

Professor Leigh is responsible for the initiation, management and exploitaton of research on the molecular basis of infectious disease.

Research Summary

Professor leigh is currently conducting research on Streptoccus uberis as a cause of bovine mastitis. This research is contained within two projects funded by BBSRC (abstracted below).

Exploitation of virulent/avirulent strain comparison to detect pathogen & host factors critical to the pathogenesis of bovine mastitis due to S.uberis (BBSRC grant number BB/E018173) Bovine mastitis is one of the most common infectious diseases of livestock animals, around 1 million cases of clinical disease occur annually in the UK. Mastitis was recognised by the Farm Animal Welfare Committee as having a major impact on the welfare of dairy cattle. Streptococcus uberis is a common cause of bovine mastitis world wide. Intramammary infection with S. uberis, unlike many other pathogens, cannot be controlled by changes to husbandry and milking-time hygiene. This project aims to exploit the presence of virulent and avirulent forms of this organism (both naturally occurring, strain EF20, and recently generated isogenic mutants of strain 0140J to both identify key virulence determinants and to determine the host responses that are associated with different aspects of disease pathogenesis. Essential virulence determinants will be identified by a combination of proteomics and comparative genomics to identify bacterial genes associated exclusively with virulent phenotype 0140J. The presence of these genes will be traced within the MLST characterised global population of S. uberis and those found to be external to the bacterial cell and common to clinical isolates will be mutated within the sequenced strain 0140J. Mutants will be characterised with respect to their virulence in a well established model of disease to establish a role for individual bacterial genes in the pathogenesis. Host responses to infection will be measured using microarrays probed with RNA derived from immune cells from the mammary gland post challenge. Comparison of responses obtained following challenge the virulent strain 0140J and the avirulent strains will permit the correlation of those responses that correspond to different aspects of pathogenesis. The output from this project will provide vital information relating to both pathogen and host that may be exploited in strategies for disease control.

The role of sortase anchored proteins in the virulence of S. uberis (BBSRC grant number S19514) Sortase (Srt) is a transamidase required to anchor proteins covalently at the surface of Gram-positive bacteria. Mutagenesis will be used to inactivate Srt activity in S. uberis. Proteomics will be used to identify proteins anchored at the bacterial surface through Srt. Interrogation of the genomic sequence will enable the orfs of Srt-anchored proteins to be identified and compared to a list of 30 putative sortase substrates, identified directly from the genome. The ability of the srt mutant to display properties associated with virulence and to induce mastitis in the target species will be determined to identify the collective role of Srt-anchored proteins in the virulence of S. uberis and the pathogenesis of bovine mastitis.

Recent Publications

School of Veterinary Medicine and Science

University of Nottingham
Sutton Bonington Campus
Leicestershire, LE12 5RD

telephone: +44 (0)115 951 6116
fax: +44 (0)115 951 6415
email: veterinary-enquiries@nottingham.ac.uk