Chlamydia trachomatis is an exclusively intracellular pathogen that can cause blindness or sexually transmitted diseases in humans, depending on the site of infection. During infection, chlamydia remodels many aspects of the host cell to its advantage, from the cytoskeleton to the Golgi apparatus. This is achieved with the use of over 70 effector proteins, which are secreted into the host cell and interact with host proteins to achieve their effects.
In eukaryotes, much of cell signalling involves intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). These are proteins that fully, or partially, lack a specific tertiary structure, and are highly flexible, exploring multiple conformations. These proteins are significantly more common in eukaryotes, but a high prevalence has also been detected on plant pathogens.
This PhD project aims to characterise intrinsically disordered effectors in chlamydia, initially by identifying disorders in effector proteins using computational tools. Relevant examples will then be chosen for experimental studies, either because of an unusual amino acid sequence that can suggest unique structural properties or because of known (but not fully characterised) interactions with host proteins of biological relevance.
Structural properties, dynamics, and interactions will be studied mainly by nuclear magnetic resonance (NMR) spectroscopy, complemented by a number of other biophysical techniques. For instance, synchrotron radiation circular dichroism (SRCD), surface plasmon resonance (SPR), isothermal titration calorimetry (ITC).
The combination of all these techniques will place the PhD candidate in a highly collaborative environment, and maximise learning opportunities.