Principal Supervisor: Dr Elizabeth Fullam, School of Life Sciences

Co-supervisor: Professor Alex Cameron

PhD project title: Structural insights into nutrient uptake in Mycobacteria – pathogens that cause TB in cattle and humans

University of Registration: University of Warwick

Project outline:

The aim of the project is to investigate the structure and mechanisms of ABC-transporters that are essential to transport nutrients in both Mycobacterium bovisand Mycobacterium tuberculosis (Mtb). Key questions that we want to know are which nutrients are recognized by these transport systems and what are the precies molecular interactions that are involved. These studies will provide a a complete molecular understanding into what mycobacteria eat and how it eats it.

The project will involve:

  1. Biochemistry – including molecular biology, protein production and characterisation
  2. Biochemistry/biophysical assays – including microscale thermophoresis/SPR/ITC
  3. Structural biology – X-ray crystallography

Mycobacterium bovisand Mycobacterium tuberculosisare the causative agents of tuberculosis (TB) in cows and humans (1). These bacterial pathogens are unusal as they are able to survive within the host for decades, during latent infection. The nutrients that they use to survive are not well understood, however recent studies in our lab (2), and by others (3), have shown that the mycobacterial ABC-transporters have a unique role in recycling nutrients from their own cell wall.

This project aims to develop molecular insights into the these important global pathogens. Long-term this may open up new strategic and/or diagnostic interventions by providing information about how to inhibit these nutrient uptake processes.

References:

  1. Davies, P. D. (2006) Tuberculosis in humans and animals: are we a threat to each other?J R Soc Med99, 539-540
  2. Fullam, E., Prokes, I., Futterer, K., and Besra, G. S. (2016) Structural and functional analysis of the solute-binding protein UspC from Mycobacterium tuberculosis that is specific for amino sugars. Open Biol6
  3. Kalscheuer, R., Weinrick, B., Veeraraghavan, U., Besra, G. S., and Jacobs, W. R., Jr. (2010) Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis. Proc Natl Acad Sci U S A107, 21761-21766

BBSRC Strategic Research Priority: Food Security

Techniques that will be undertaken during the project:

Key experimental skills involved:

Contact: Dr Elizabeth Fullam, University of Warwick