Cell envelope synthesis in Gram-positive bacteria: mechanisms, regulation and inhibition

The bacterial cell wall is an essential, highly conserved structure. It is the target for our best antibiotics and is recognised by the innate immune system as a signal for infection. Many mechanistic details of cell wall synthesis remain unsolved, especially how it is regulated spatially and temporally. Firmicutes and Actinobacteria represent ancient groups of bacteria that have evolved contrasting mechanisms to grow with a rod shape.

I will use genetic, biochemical and imaging methods to study components of the Bacillus subtilis cell wall elongation machinery and compare this with the tip extension and branching behaviour of a rare related group of bacteria called Thermoactinomycetes.

The results will help us understand wall synthesis in more global and mechanistic terms and illuminate how wall synthesis regulation evolved. I will use the information that emerges in early stage screening for potential antibiotics with novel actions that target the cell wall.