How does metabolic heterogeneity drive antibiotic tolerance/resistance in Mycobacterium tuberculosis

Summary: Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of infectious death globally. Alternative TB treatments are urgently required to counter the global spread of drug resistance that is thwarting the control of tuberculosis. The goal of this PhD research project is to develop methods to study metabolic heterogeneity and its impact on the development of antibiotic tolerance/resistance. A detailed understanding of these processes will guide potential new treatment strategies and the development of new drugs

This inter-disciplinary PhD project will apply a state-of-the-art experimental approaches to test our hypothesis that metabolic heterogeneity plays a pivotal role in determining antibiotic efficacy.

Impact: The results from these studies will guide potential new treatment strategies desperately needed to control the ongoing tuberculosis pandemic. This work can also be applied towards new understanding of how cells function, infectious disease, metabolic engineering, and beyond.

Skills: Training will be provided in several areas of mycobacteriology, molecular biology, including working at containment level 3 and state-of-the-art bioanalytical chemistry in research groups which have an excellent track record of success in these areas. The student will become an active member of the tuberculosis research community at the University of Surrey attending meetings, journal clubs and presentations and will benefit from mentorship from other research scientists here. Additional opportunities will include bespoke training courses, a scientific writing retreat, public outreach events and support to present their research at conferences, all of which will facilitate future career development.

The University of Surrey and our collaborative partners provide a vibrant, interdisciplinary research environment, with access to state-of-the-art facilities.  We see our postgraduate researchers as an integral part of our research community, collaborating and innovating together with academics at all levels. We want the most talented researchers from diverse backgrounds to join us, bringing new ideas and perspectives. We will help you make the most of your potential, removing barriers where we can and supporting you with dedicated career guidance. We offer generous funding packages, sector-leading researcher development training and mentoring, and dedicated employability support.

Whatever your aspirations, Surrey is where research careers are launched and nurtured.

Applicants are expected to hold a good honours degree (upper second) in an appropriate discipline, but prior experience in research or industry may be acceptable. Enthusiasm for, and commitment to, independent study is essential.

English Language requirements 

IELTS Academic: 6.5 or above (or equivalent) with 6 in each individual category.

Section of Bacteriology

Relevant publications

Borah, K. et al. Metabolic fluxes for nutritional flexibility of Mycobacterium tuberculosis. Mol Sys Biol 17, e10280, doi:https://doi.org/10.15252/msb.202110280 (2021).

Basu, P. et al. The anaplerotic node is essential for the intracellular survival of Mycobacterium tuberculosis. J Biol Chem 293, 5695-5704, doi:10.1074/jbc.RA118.001839 (2018).

Borah, K. et al. Intracellular Mycobacterium tuberculosis Exploits Multiple Host Nitrogen Sources during Growth in Human Macrophages. Cell Rep 29, 3580-3591 e3584, doi:10.1016/j.celrep.2019.11.037 (2019).

de Jesus, J. M. et al. Correlative Imaging of Trace Elements and Intact Molecular Species in a Single-Tissue Sample at the 50 μm Scale. Analytical Chemistry 93, 13450-13458, doi:10.1021/acs.analchem.1c01927 (2021).

Lewis, H.-M. et al. Nanoextraction Coupled to Liquid Chromatography Mass Spectrometry Delivers Improved Spatially Resolved Analysis. Analytical Chemistry 91, 15411-15417, doi:10.1021/acs.analchem.9b02821 (2019).