Antibiotic production and cellular development in bacteria are intimately linked to the extracellular environment.
One key mechanism by which bacteria recognise and respond to these external cues is through two-component regulatory systems (2CS). Consisting of a membrane-bound sensor kinase and a partner DNA-binding response regulator, these 2CSs are essential in the response to a myriad of signals including antibiotic attack, microbial interaction and nutrient availability.
The soil-associated filamentous Actinobacteria Streptomyces spp. are prolific antibiotic producers with a large number of 2CSs. A new developmental stage has recently been described termed exploration whereby the colony rapidly expands via non-branching vegetative hyphae, a juxtaposition to the complex canonical lifecycle which ends in sporulation. 15 of the 58t 2CS in the model organism Streptomyces venezuelae are highly conserved throughout Streptomycetaceae.
Thomas’ project focuses on understanding how these highly-conserved 2CSs regulate antibiotic production and cellular development in streptomycetes with a view on using this knowledge to discover new antibiotics.