The Bloomsbury Colleges | PhD Studentships | Studentships 2014 | Structural, Functional And Genetic Studies Of The Proteins Of The Bkar Regulon Of M.Tuberculosis, Probably Involved In Leucine Degradation.
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Structural, Functional And Genetic Studies Of The Proteins Of The Bkar Regulon Of M.Tuberculosis, Probably Involved In Leucine Degradation.

Principal Supervisor: Prof Nicholas Keep (Birkbeck)

Co- Supervisor: Dr Sharon Kendall (Royal Veterinary College)

Tuberculosis remains the single biggest killer infection, particularly when coupled with HIV/AIDS infection. The biology of the causative organism, Mycobacterium tuberculosis (Mtb), has benefited from the genome sequence for nearly 20 years. Nevertheless many of the details of its metabolism and gene regulation remain inferred from similarities from better studied organisms such as Escherichia coli or even human metabolism. This means although general function can be assigned to a set of related genes, ascribing a gene to a particular pathway is problematic. This is particularly true of the genes of fatty acid metabolism which are heavily enriched in M. tuberculosis compared to many organisms. This project brings together complementary skills from the RVC and Birkbeck. Prof Keep has extensive experience in structural and enzymatic studies of Mtb proteins(1), along with work on fatty acyl-coA metabolism going back to his PhD (2). Dr Kendall brings extensive experience in gene regulation in Mycobacteria (3,4). Together we wish to unravel the function of the genes controlled by the BkaR regulator (Rv2506), which has been shown to be important for the survival of the bacteria in macrophages.  Macrophage infection is a crucial state in the infectivity of the MTb pathogen.  The work will be divided between biochemical and genetic studies of the regulator at the RVC and structural and enzymatic studies of the enzymes of the pathway at Birkbeck.  The student will join the 2014-15 BBSRC DTP cohort for training and monitoring.

Candidate requirements

Good First degree in Biochemisty, Microbiology, or other Molecular Biology discipline.

Key References

  1. Chauviac F.-X., Bommer, M., Yan, J., Parkin, G., Daviter, T., Lowden, P., Raven, E.L.,Thalassinos, K., & Keep, N.H (2012) Crystal Structure of Reduced MsAcg, a PutativeNitroreductase from Mycobacterium smegmatis and a Close Homologue of Mycobacterium tuberculosis Acg J. Biol. Chem. 287, 44372–44383.
  2. Keep, N.H., Smith, G.A., Evans, M.C.W., Diakun, G.P. and Leadlay, P.F. (1993). The synthetic substrate succinyl(carbadethia)-CoA generates cob(II)alamin on adenosylcobalamin-dependent methylmalonyl-CoA mutase. Biochem. J. 295:387-392.
  3. Balhana, RJC, Swanston, SN, Coade, S, Withers, M, Sikder, MH, Stoker, NG and Kendall, SL (2013) bkaR is a TetR-type repressor that controls an operon associated with branched-chain keto-acid metabolism in Mycobacteria FEMS Micro. Letts. 345, 132-140
  4. Kendall SL, Burgess P, Balhana R, Withers M, Ten Bokum A, Lott JS, Gao C, Uhia-Castro I, Stoker NG: Cholesterol utilization in mycobacteria is controlled by two TetR-type transcriptional regulators: kstR and kstR2. Microbiology 2010, 156(Pt 5):1362-1371

Principal Supervisor: Nicholas Keep, n.keep@mail.cryst.bbk.ac.uk, http://people.cryst.bbk.ac.uk/~ubcg48a/

Co- Supervisor: Sharon Kendall, skendall@rvc.ac.uk, http://www.rvc.ac.uk/Staff/skendall.cfm

Further information about PhDs at Birkbeck is available from:

http://www.bbk.ac.uk/biology/phd/studentships

Application forms and details about how to apply are available from:

https://cis.bbk.ac.uk/apex/f?p=E2:LOGIN:::::PRO,CODE1,CODE2:IPPAPP,RMPBIOLG,6011

http://www.bbk.ac.uk/study/2014/phd/programmes/RMPBIOLG/

PhD Administator t.hoe@mail.cryst.bbk.ac.uk  , 020-7631-6800

The student should indicate an interest in this project in the application form.

Closing date for applications is 10th February 2014