Infection, Immunity, Antimicrobial Resistance & Repair MRC GW4 BioMed DTP PhD studentship 2025/26

Summary

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a devastating infectious disease causing over one million human deaths every year. We urgently need new drugs/therapies to fight the accelerating problem of drug resistance in TB. Oxygenated sterols: oxysterols and oxygenated lipids: oxylipins are biologically important molecules in metabolism, infection and immunity and are emerging new targets for anti-TB drug development. However, the precise role of these molecules in infection is not clear. This project will investigate which oxysterols and oxylipins are important in TB and how they boost human host’s defence against the pathogen to provide new drug target.

Description

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a devastating infectious disease causing over one million human deaths every year. TB treatment is complicated by the rapidly rising cases of drug resistance and therefore, we urgently need new treatments to fight drug-resistance and stop TB.

Oxygenated sterols called “oxysterols” and oxygenated lipids called “oxylipins” are biologically important molecules that can be generated by the cytochrome P450 pathways and/or reactive oxygen species (ROS) autooxidation pathways. These biomolecules are important in infection and immune response against the pathogenic Mtb and are attractive targets for new therapeutic development. However, our knowledge about the role of these molecules in human host and Mtb, and host-pathogen interactions are not clear.

The lead supervisor’s research has demonstrated that the levels of oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol are significantly reduced in the serum of patients with active pulmonary TB disease when compared to healthy individuals. In case of patients with extrapulmonary TB, the levels of these oxysterols are significantly elevated (~10-fold) when compared to the healthy individuals.

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