Wilkinson lab

Tuberculosis Laboratory

: Areas of interest

Mycobacterium tuberculosis is readily transmissible and thereby causes 10 million cases and 1.3 million deaths from tuberculosis (TB) per year: the leading infectious cause of death globally. 

A paradox is that ~90% people develop partial or even complete immunity to TB. Understanding this would provide opportunities to more accurately prognosticate, better vaccine design and potentially other inventions to augment immunity.

If replication is not controlled, much of the pathology is caused by the immune system itself. This raises the possibility of using adjunct treatments in addition to antimicrobial therapy. Both questions are incompletely answered by existing knowledge, but information on each has already informed clinical practice.

The program capitalises on unique infrastructures that bring together real-world clinical studies and clinical trials, state of the art clinical imaging, and platforms for molecular and cellular analyses. 

As with much clinical research, much of the work is of necessity associative, but to better resolve causality, the program benefits from detailed phenotyping of individuals undergoing inventions in the context of clinical trials, large cross-sectional studies and well-characterised cohorts studied longitudinally.

The underlying hypotheses are:

1. As most humans do not progress to TB, there are critical and common, but overlooked, T cell functions that contribute to containment and even eradication of infection.
2. Failure of control results in a progressive inflammatory cascade leading to neutrophil recruitment that is a major determinant of necrotic pathology in the lungs, and following dissemination to other organs.
3. In the most severe meningeal form of tuberculosis inflammation not only causes damage directly, but sets up deranged metabolism that contributes to ongoing injury.
4. That delineation of protective and pathogenic pathways can guide 
   a)    more effective vaccination and 
   b)    more specific and powerful adjunctive anti-inflammatory therapies to ameliorate death and disability.