How do you build a wall? Mechanistic principles of bacterial division septum building (360G-Wellcome-227452_Z_23_Z)

The goal of this proposal is to determine the molecular, mechanistic and biophysical principles by which proteins build and close the bacterial cell division septum, using Gram-positive Bacillus subtilis as a principal model organism. This project will reveal how bacteria spatially coordinate cell envelope remodelling to build and close their division septum, will identify novel functional and regulatory roles of highly conserved bacterial cell division proteins and aims to identify new proteins with major roles in septal closure. This will be achieved by exploiting multi-disciplinary approaches including super-resolution microscopy, electron cryo-tomography, cellular scale coarse-grained molecular simulation, bacterial genetics and molecular microbiology. We will realise these goals via four linked aims: \- Aim 1. How is the nanoscale activity of individual divisome synthesis complexes regulated? \- Aim 2. How does the cytoskeleton coordinate septum building on the microscale? \- Aim 3. What are the key mechanistic principles of septal closure? \- Aim 4. Which proteins specifically mediate septal closure? By providing crucial mechanistic information our work will, we believe, support ongoing world-wide efforts to find new antibiotic inhibitors of bacterial cell division.