Dr A Bhatt, Prof Robin May
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
Sequenced genomes of mycobacteria, including the bovine TB pathogen Mycobacterium bovis and it’s ‘cousin’ the human pathogen Mycobacterium tuberculosis, reveal a number of genes dedicated to lipid biosynthesis and transport. These unique lipids confer a distinct quality to the mycobacterial cell wall, and play an important role in adhesion, immunomodulation and virulence. Research in the lab over the last 5 years has focussed on deciphering the genetic pathways that define lipid biosynthesis and transport in pathogenic mycobacteria 1-5. With the use of defined mutant strains defective in the production of relevant lipid species, we plan to test the molecular mechanisms underlying the processes of lipid mediated:
1) adhesion and invasion.
2) survival inside infected macrophages.
3) modulation of the immune system.
Additionally, we would also like to exploit lipid biosynthesis-related mycobacterial enzymes and transporters as potential drug targets, by gaining insights into their structure for drug interaction studies.
Key experimental skills involved:
The project involves a mix of genetics, molecular studies and biochemical analysis. Infection related experiments will also involve cell biology. Molecular studies will include the expression and purification of proteins, site directed mutangenesis, bacterial genetics (mutant construction) and biochemical analysis of the mycobacterial cell wall.
Explain how the project can incorporate “new ways of working” (ie. quantitative biology, 'omics, systems biology, integrative biology, high throughput analysis, synthetic biology etc.).
The project combines a number of approaches, including bacterial genetics, bioinformatics, biochemistry, structural biology and biophysical methods to address the above mentioned research questions. The existing high throughput drug screening facility at the School of Biosciences presents an opportunity for screening potential drug candidates that interfere with MmpL-mediated transport processes. Furthermore, the availability of a BSL3 facility in the IBR (and soon in Biosciences) allows us to carry out work on both M. tuberculosis and M. bovis.
Funding Notes
This studentship is competition funded by the BBSRC MIBTP scheme: http://www.birmingham.ac.uk/research/activity/mibtp/index.aspx
Deadline: January 31, 2015
Number of Studentships available: 30
Stipend: £ 13,726 per annum (plus £600 travel allowance in year 1, and a MacBook Pro)
The Midlands Integrative Biosciences Training Partnership (MIBTP) is a BBSRC-funded doctoral training partnership between the universities of Warwick, Birmingham and Leicester. It delivers innovative, world-class research training across the Life Sciences to boost the growing Bioeconomy across the UK.
To check your eligibility to apply for this project please visit: http://www2.warwick.ac.uk/fac/cross_fac/mibtp/pgstudy/phd_opportunities/application/
References
(1) Varela C., Rittmann D., Singh A., Krumbach K., Bhatt K., Eggeling L., Besra G.S. and Bhatt A. (2012) MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria. Chem Biol 19:498-506.
(2) Sarkar D., Sidhu M., Singh A., Chen J., Lammas D.A., van der Sar A.M., Besra G.S. and Bhatt A. (2011) Identification of a glycosyltransferase from Mycobacterium marinum involved in the addition of a caryophyllose moiety in lipooligosaccharides. J Bacteriol 193:2336-2340.
(3) Khan S., Nagarajan N.S., Parikh A., Samantaray S., Singh A., Kumar D., Roy R.P., Bhatt A. and Nandicoori V.K. (2010) Phosphorylation of enoyl-ACP reductase InhA impacts mycobacterial growth and survival. J Biol Chem 285: 37860-37871.
(4) Chen J., Kriakov J., Singh A., Jacobs Jr. W.R., Besra G.S. and Bhatt A. (2009) Defects in glycopeptidolipid biosynthesis confer phage I3 resistance in Mycobacterium smegmatis Microbiol 155: 4050-4057.
(5) Bhatt A., Brown A.K., Singh A., Minnkin D.E. and Besra G.S. (2008) Loss of a mycobacterial gene encoding a reductase leads to an altered cell wall containing -oxo-mycolic acid analogs and accumulation of ketones. Chem Biol 15: 930-939.
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