Bovine and human TB: probing the genetic, molecular and structural basis of lipid-mediated pathogenesis mechanisms.

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

Tuberculosis is one of the greatest causes of death due to an infectious disease worldwide (joint with HIV). It is caused by members of the Mycobacterium tuberculosis (MTB) complex, which demonstrate 99.9% similarity at a nucleotide level (Boddinghaus, B. et al., 1990) yet differ greatly in their host trophism and pathogenicity. This project will focus mainly on the evolution of members of the MTB complex. One approach will involve delineating differences between two members, Mycobacterium tuberculosis (M. tuberculosis) and Mycobacterium bovis (M. bovis) through the generation of knockout recombinant strains that represent intermediates in the evolution of these pathogens; these strains will be employed in infection studies. A second approach involves the utilisation of differing cell lines in similar infection studies, due to the tissue trophism observed during mycobacterial infection. Finally, a third approach will involve delineating the fundamental processes that drive pathogenicity, to determine the differences between non-pathogenic environmental pathogens from pathogenic members of the MTB complex.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1644258 Studentship BB/M01116X/1 05/10/2015 30/09/2019 Hayleah Pickford
 
Description Cell biology of bovine TB macrophage interactions and evolution of the bovine TB bacillus 
Organisation Francis Crick Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Generation of recombinant 'MTB-like strains of the bovine TB bacillus and assessing lipid profiles of the same.
Collaborator Contribution Comparing and contrasting infection bovine and human macrophages by MTB and bovineTB bacilli. Transcritpomics of MTB-like M. Boris strains.
Impact None yet.
Start Year 2016
 
Description Cell biology of bovine TB macrophage interactions and evolution of the bovine TB bacillus 
Organisation University College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution Generation of recombinant 'MTB-like strains of the bovine TB bacillus and assessing lipid profiles of the same.
Collaborator Contribution Comparing and contrasting infection bovine and human macrophages by MTB and bovineTB bacilli. Transcritpomics of MTB-like M. Boris strains.
Impact None yet.
Start Year 2016
 
Description Role of lipids in Mycobacterium tuberculosis-host interactions 
Organisation University of Minho
Country Portugal 
Sector Academic/University 
PI Contribution Dr.Saraiva will benefit from access to mutants from Dr.Bhatt's lab and to lipid extraction methodologies. In the future the project could expand to include animal models of infection.
Collaborator Contribution Dr.Bhatt has the opportunity to expand his projects to include TB-immunology via the specialised expertise of Dr.Saraiva.
Impact Successful application for a Royal Society International Exchanges Award.
Start Year 2013