Studying the role of MreCD complex in its modulation of the Elongasome

The bacterial cell envelope is crucial for protecting the cell and enabling its pathogenicity, serving as the first line of defence against antibiotics, phages, and toxins. It consists of a complex assembly of proteins, sugars, and lipids that also help maintain the cell's structure and shape. A key component is the extracellular cell wall, a mesh-like structure targeted by many antibiotics. Understanding how this wall is built and maintained is vital for developing new antibacterial strategies. This project uses advanced interdisciplinary methods to study the proteins involved in the formation of the bacterial cell wall.

Two important proteins, MreC and MreD, play roles in regulating cell wall growth, but their exact functions are not fully understood. Recent studies suggest that while MreC promotes cell wall growth, MreD might inhibit it. Both proteins are components of a larger macromolecular system, called the Elongasome, a key player in cell wall synthesis during cell growth, but the details of these interactions remain unclear. Our recent findings suggest that MreC and MreD form a complex that likely interacts with PBP2, yet the structural and dynamic aspects of these interactions are still unknown.

In this project, we will use AlphaFold to predict the structures of the Elongasome in the context of MreC and MreD, and employ molecular dynamics simulations to explore how these proteins behave within the cell membrane. Following from this, we will test computational predictions in an experimental setting using a range of protein biochemistry techniques to measure protein-protein and/or protein-substrate interactions informing on structural and as well as functional biology of the elongasome.

This research addresses the urgent need to understand bacterial mechanisms of growth, which is key to developing new antibiotics. The project is highly interdisciplinary, combining computational biology, molecular modelling, protein and structural biochemistry. Through this work, the project will employ cutting-edge techniques such as protein modelling, molecular dynamics simulations, and computational analysis.