Structure, Function and Biogenesis of the Mycobacterial Cell Wall

There has been no significant decrease in worldwide mortality due to tuberculosis (TB) since before the time of Koch; the advent of sanatoria and chemotherapy, which drastically reduced TB in the more developed countries, has had no profound effect on the global problem. The reasons for the transient increase have been well documented: the HIV/AIDS epidemic, increased immigration and transmission from high-prevalence countries, and the emergence of multi-drug resistant strains of TB. We (GSB) have contributed over the past several years in understanding the characteristics of the cell wall of TB, which has been the site of action of a number of front-line TB agents. We have now opted for a broader strategy: identification of new drug targets and drug development (with Professor Minnikin); vaccine development; identification of mechanisms of intracellular survival, replication and pathogenesis; definition of the fundamental genome of the tubercle bacillus, its phenotype and the functionality of the phenotypic characteristics through derivation of mutants. It is a widely held view that efforts to relieve the disease burden imposed by tuberculosis must benefit from concerted attempts to understand the basic biochemistry of the organism, particularly in view of the current availability genomic data from the M. tuberculosis genome. Thus, providing a timely insight into these remarkable bacteria and several novel areas of mycobacterial cell wall physiology.

A mixture of genetic, biochemical and chemical approaches will be used in the projects outlined below, and applications from students with a chemical, biochemical or molecular genetics background are encouraged.

1. To advance understanding of the biosynthesis and regulation of mycolic acids and to pinpoint the mechanism(s) of action of existing and novel inhibitors of thereof.
2. To identify and characterise the specific glycosyltransferases and regulatory mechanisms involved in the biosynthesis of arabinogalactan and lioparabinomannan.
3. To identify key intermediates in the assembly of the peptidoglycan component of the mAGP complex and characterise their metabolic flux in the presence and absence of known and novel beta-lactam agents.
4. To advance and apply methods for the ultra-sensitive detection and characterisation mycobacterial lipids acids as biomarkers of tuberculosis in ancient bones.
6.To advance understanding of the new cellular pathway leading to T cell activation by lipid and glycolipid antigens presented by CD1 proteins.

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To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each school, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at: www.birmingham.ac.uk/students/drp.aspx
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Please find additional funding text below. For further funding details, please see the ‘Funding’ section.
The School of Biosciences offers a number of UK Research Council (e.g. BBSRC, NERC) PhD studentships each year. Fully funded research council studentships are normally only available to UK nationals (or EU nationals resident in the UK) but part-funded studentships may be available to EU applicants resident outside of the UK. The deadline for applications for research council studentships is 31 January each year.

Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also 31 January each year.