My research involves an in-depth characterisation of nucleotide signalling systems in the Gram-positive pathogen Staphylococcus aureus. S. aureus is a human pathogen responsible for a vast array of disease and morbidity worldwide, a problem that is exacerbated by the spread of antibiotic-resistant strains such as methicillin resistant S. aureus (MRSA).
When this bacterium invades a human host it encounters a number of different stresses, such as nutrient limitation. The bacteria respond to these stresses by switching on a nucleotide signalling system called the stringent response.
This response results in the synthesis of two small nucleotides, collectively referred to as (p)ppGpp, which can be made in the cell by three different enzymes – RSH, RelP and RelQ. These nucleotides are the effectors of the stringent response and function by binding to target proteins leading to the bacterial cells shutting down active growth and entering a persistent state that promotes survival.
My previous research has led to the development of a genome-wide approach to analyse nucleotide-protein interactions. The current focus of the lab is on utilising this methodology, in conjunction with biochemical assays, to identify binding targets for (p)ppGpp in S. aureus in order to precisely map how these nucleotides function in a bacterial cell.
By mapping of the (p)ppGpp signalling network this research will provide key insights into the functioning of (p)ppGpp and so generate important mechanistic data on the pathogenesis of S. aureus.