Role of the lysosome, and the lysosomal protein NPC1 in the pathogenesis and treatment of Mycobacteriumtuberculosis
Tuberculosis (TB) is a chronic disease that in it’s latent form affects approximately one third of the worlds population with an estimated 10 million new cases and 1.5 million deaths per year.
With an ever increasing number of multidrug resistant TB cases (~500,000 in 2014) it is clear that new pharmaceutical strategies are required to treat TB. My laboratory works on lysosomal storage diseases and we have identified that a lysosomal transmembrane protein called NPC1 is a target of cell wall lipids secreted by Mycobacterium tuberculosis (MTb). The NPC1 protein is one of the only eukaryotic members of a prokaryotic family of multi substrate efflux pumps called RND permeases. We believe that MTb utilises this similarity to secrete lipids via its own family of RND permeases that ultimately inhibits NPC1 function which leads to a block in phago-lysosome fusion and a failure to clear MTb by the host macrophage. The aim of this PhD is to fully characterise this novel component of MTb pathogenesis so that we may develop new treatments for TB, ideally ones that boost host NPC1 function.
Techniques – Microbiology, cell biology, molecular biology, histology.