Chlamydia is a bacterial obligate intracellular parasite which extensively modifies the host cell for its own advantage during infection. This is achieved through effectors, proteins that are produced by chlamydia and injected into the host cell. Once inside the host cell, the effectors interact with host proteins to alter the cell cytoskeleton. metabolism, survival and other parameters, providing optimal growth conditions for the parasite. This PhD project aims to study these molecular interactions to understand how chlamydia modifies the cell at a molecular level.
We have shown that Tarp, an intrinsically disordered protein from chlamydia, has a partially formed helix which is stabilised when bound to an actin monomer. This disorder-to-order transition is part of the process that leads to the nucleation of new actin filaments in the beginning of the cell invasion process, forming an actin pedestal which brings chlamydia into the cell. This PhD project intends to look at other chlamydia effectors and their interactions with host cell proteins. For instance, TmeA interacts with N-WASP to contribute to cytoskeleton remodelling, CT229 interacts with the cell signalling proteins to help establish the chlamydial inclusion, and CT166 mediates actin depolymerisation.
Chlamydia is the main cause of preventable blindness in the world (trachoma) and is responsible for the most diagnosed sexually transmitted disease in the UK – which can result in infertility. To infect cells and cause disease, chlamydia produces a very large number of effectors which affect the host cell in many different ways. While chlamydia infections are currently treatable with antibiotics, there are early signs of emerging resistance. Understanding the mechanisms of such a pathogen will allow us to find new targets for drug therapies. At the same time, the multiple cellular pathways explored by chlamydia can also be targeted by other pathogens, so their characterisation will have wider application.
The PhD candidate will receive training in protein expression and purification, protein NMR spectroscopy, and a number of biophysical techniques for studying protein interactions.
