Active Cells, Biochemistry & Physiology Infection & Immunity

How do you build a wall? Mechanistic principles of bacterial division septum building

Funder Wellcome Charity-funded
Associated organisations Institute of Science and Technology Austria · MRC Laboratory of Molecular Biology · University of Warwick Europe PMC affiliations are not treated as award recipients or mapped locations.
Funding £3.5M
Period Jan 2024 — Jan 2032

In plain English

AI plain-English summary

A bacterium building its division wall is a nanoscale construction site, and this project will map every molecular worker and their tools. Bacteria divide by pinching themselves in two, building a wall—the septum—across their middle. If this process fails, the cell dies. Many of our most effective antibiotics, like penicillin, work by jamming this wall-building machinery. But bacteria are evolving resistance, and we are running out of drugs that target this process. The problem is that we still do not understand, at a fundamental mechanical level, how the dozens of proteins involved coordinate their actions to build and close the septum. This project will use Bacillus subtilis as a model to answer four specific questions: how individual synthesis complexes are regulated, how the cytoskeleton coordinates construction, what principles govern the final closure, and which proteins specifically mediate that closure. This is fundamental science. It will not produce a new antibiotic tomorrow. But by revealing the precise molecular choreography of septum building, it provides the mechanistic blueprint that drug developers need to design the next generation of antibiotics. Without this basic understanding, efforts to find new inhibitors are essentially guessing in the dark.

View original technical description
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.

View the original record at the funder ↗

Researchers

Andela Saric (EPMC Awardee)Jan Löwe (EPMC Awardee)Séamus Holden (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Super-resolving the physical mechanisms of bacterial cell division
Deconstructing energised associations that build and maintain the Gram- negative Bacterial Cell Envelope
Architecture of the bacterial divisome.
Combining cutting edge molecular microbiology and super-resolution microscopy to reveal how bacteria divide, and how to stop them
Communicating across the membrane during bacterial cell division

Original classification

Discovery Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.