Splitting spores: understanding how alarmone signalling controls bacterial sporulation

Sporulation is the fascinating process by which some bacterial species can differentiate into a metabolically inert form that can survive incredibly harsh environmental conditions. The spore forming Clostridia include a large number of important pathogens of both animals and humans, food spoilage organisms and species that are commonly used in industrial biotechnology.

Sporulation is absolutely essential for the survival of these species, but we know surprisingly little about how it is controlled.

We have recently shown that sporulation in Clostridioides difficile is affected by the stringent response, a near ubiquitous nucleotide signalling circuit in bacteria. This project will leverage our groups' expertise and tools for nucleotide signalling (Corrigan1,3) and Clostridial cell biology (Fagan2,4) to dissect this regulatory pathway in C. difficile and combine this with sophisticated microscopy to understand the impacts on cell differentiation.

We will identify the points of interaction between the sporulation pathway and the stringent response, decipher the environmental signals that lead to its activation and identify the proteins and regulatory pathways in the cell that respond to the central stringent response nucleotide ppGpp.