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Protein kinases and nitric oxide in the stealthy survival of Mycobacterium tuberculosis


About This PhD Project

Project Description

Tuberculosis remains a major global threat as it affects humans and production animals. Mycobacterium tuberculosis and Mycobacterium bovis, the causative agents of tuberculosis in human and animals, are highly successful pathogens which have sophisticated mechanisms for adaptation to hostile conditions. Nitric oxide (NO) has been long implicated in triggering dormancy in mycobacteria, while serine threonine protein kinases PknB and PknG have been shown to be critical for reactivation from dormancy and regulation of central metabolism. We have recently established that treatment of M. tuberculosis with NO resulted in significant up-regulation of PknB and PknG as well as CwlM and SigH, PknB substrates. Furthermore, we found that over-expression of CwlM stimulated M. tuberculosis survival in activated macrophages. These findings suggest that PknB-mediated phosphorylation is important for mycobacterial survival under nitrosative stress and during macrophage infection. Moreover, PknG is essential for virulence and survival in dormancy.
The proposed project will be focused on investigation of PknB and PknG interplay in NO-treated mycobacteria and during recovery from nitrosative stress. We will also study how depletion of PknB and PknG (as well as their over-expression) impact on mycobacterial survival.

Eligibility:
UK/EU applicants only.

Entry requirements:
Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better in a relevant subject.
The University of Leicester English language requirements apply where applicable: https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

How to apply:
Please refer carefully to the application guidance and apply using the online application link at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

Project / Funding Enquiries:
Application enquiries to
Closing date for applications: Sunday 12th January 2020

References

Turapov et al. Two Faces of CwlM, an Essential PknB Substrate, in Mycobacterium tuberculosis. Cell Rep. 2018 Oct 2;25(1):57-67. e5. doi: 10.1016/j.celrep.2018.09.004. https://www.sciencedirect.com/science/article/pii/S2211124718314190?via%3Dihub

Rieck et al. PknG senses amino acid availability to control metabolism and virulence of Mycobacterium tuberculosis. PLoS Path. 13(5): e1006399. https://doi.org/10.1371/journal.ppat.1006399 http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006399

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