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Mechanisms of growth and virulence in Mycobacterium tuberculosis and other pathogenic mycobacteria


   School of Biosciences

   Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

Sequenced genomes of mycobacteria, including the human tuberculosis causing 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 biofilm formation, adhesion, immunomodulation and virulence. Research in the lab in the past has focused on deciphering the genetic pathways that define lipid biosynthesis and transport in pathogenic mycobacteria. We now make use of systems-based approaches to outline regulatory pathways that drive growth and cell wall biogenesis. With the use of defined mutant strains, we plan to test the molecular mechanisms underlying the following processes, and their impact on virulence using experimental models of infection:

1) Factors driving the growth of pathogenic mycobacteria.

2) Regulation of cell wall biogenesis and its effect on virulence.

3) Molecules that drive biofilm formation


References

(1) Dokic A, Peterson E, Arrieta-Ortiz ML, Pan M, Di Maio A, Baliga N, Bhatt A. (2021) Mycobacterium abscessus biofilms produce an extracellular matrix and have a distinct mycolic acid profile. Cell Surf 7:100051.
(2) Pickford H, Alcock E, Singh A, Kelemen G, Bhatt A. (2020) A mycobacterial DivIVA domain-containing protein involved in cell length and septation. Microbiology (Online ahead of print)
(3) Javid A, Cooper C, Singh A, Schindler S, Hänisch M, Marshall RL, Kalscheuer R, Bavro VN, Bhatt A. (2020) The mycolic acid reductase Rv2509 has distinct structural motifs and is essential for growth in slow-growing mycobacteria. Mol Microbiol 113(2):521-533.
(4) Peterson, E. J., Bailo, R., Rothchild, A. C., Arrieta‐ortiz, M. L., Kaur, A., Pan, M., Mai, D., Abidi, A. A., Cooper, C., Aderem, A., Bhatt, A*. & Baliga, N. S.* Path-seq identifies an essential mycolate remodeling program for mycobacterial host adaptation. (2019) Mol Sys Biol 15, e8584.*Joint corresponding authors

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