The Team

I am a biological physicist who combines theoretical and computational modelling of bacterial growth and antibiotic response with laboratory experiments. I lead the model development part of the project. We are developing phenomenological models for the physiological response of growing bacteria to cell wall targeting antibiotics. We are also developing mechanical models for peptidoglycan and how it may be disrupted by cell wall targeting antibiotics.

Antibiotics are typically considered as having a specific target and molecular model of action, which they do! However by affecting the cell so significantly at one point, they also impact much of the rest of a cell's activity, especially the processes that arise at a "systems" level, such as regulation of division, crowding and chromosome conformation, which combine so many cell factors together. These systems level processes are essential to the life of a cell, so understanding them better provides an angle in addressing mechanisms of antimicrobial resistance. Our main tool is single cell live imaging.

The cell wall is essential for bacterial life and its synthesis is the target of crucial antibiotics such as penicillin and vancomycin. We determine the structure and function of the cell wall to elucidate not only how it permits cell growth but also how antibiotics lead to death. We use the infamous “super bug” Staphylococcus aureus as our target organism to address key fundamental questions of bacterial life and death. Our primary goals are to:

- determine the molecular structure of the cell wall and how it changes during growth, at a resolution never previously achieved in any organism, using our world leading microscopy approaches.

- use this information to then establish how the cell wall acts as the interface between a cell and its environment.

- bring together our findings to establish the basic mechanisms underpinning growth, the action of antibiotics and antibiotic resistance across bacteria.

My group uses and develops atomic force microscopy (AFM) to understand living systems, with a major focus on the bacterial cell wall. We have recently developed a number of approaches for imaging and mechanically probing both live bacteria and extracted cell walls with resolution down to the molecular level, and have used these in collaboration with the Foster lab to reveal the cell wall architecture and the impact of wall targeting antibiotics.

Within the Physics of AMR project, my Research Associate Abimbola Feyisara Olulana and I, in collaboration with our partners in Cambridge, Edinburgh, Newcastle and Sheffield, work to unravel the molecular and physical mechanisms enabling antimicrobial drug resistance in the human pathogens E. coli and S. aureus.

My group works on the structure of the bacterial cell wall and the molecular mechanisms of peptidoglycan synthesis during growth and cell division in a range of different bacteria. We use a range of molecular biology methods to determine the composition of the cell wall and decipher the activities and interactions of peptidoglycan synthases and hydrolases. Within the Physics of AMR project, my Research Associate Dr Jacob Biboy and I collaborate with our partners at Cambridge, Edinburgh and Sheffield to study the molecular and physical mechanisms underlying antimicrobial drug resistance in Escherichia coli and Staphylococcus aureus.

My lab works on molecular mechanisms of gene expression. In this project we try to understand why MRSA phenotype requires mutations in RNA polymerase. We purify and study these RNAPs biochemically. We also investigate the possible differential effects of global regulator Spx on MRSA RNAPs. In parallel we study antibiotics targeting transcription, which have new modes of action and lesser chance of leading to resistance.

At the Centre for Bacterial Cell Biology, my work primarily focusses on the Bacterial cell wall architecture and composition, Biochemistry of cell wall related enzymes and the molecular mechanisms of cell wall synthesis during bacterial growth and division. In this project, I will be working on the antibiotic induced changes to the cell wall of model bacteria Escherichia coli.

The main goal of my work is to identify the mechanisms of resistance to cell wall targeting antibiotics in Staphylococcus aureus. I am also interested in studying physiological differences between antibiotic-resistant and sensitive bacteria.

Rebecca Brouwers finished her PhD in 2019 and worked as a postdoc on my UKRI-funded project in 2019-20 to understand the biophysics of bacteria that are resistant to cell-wall targeting antibiotics. Rebecca's PhD work investigated the response of E. coli bacteria to cell wall-targeting antibiotics.

I have been engaged in high resolution mapping of the nano-mechanical properties of bacterial cell walls (Staphylococcus aureus) using atomic force microscopy, as well as the automation and improvement of subsequent mechanical data analyses.

In their >3 billion years evolutionary history, bacteria developed exceptional survival tools, the expression of which they can now tune according to environmental conditions. These adaptations however come at a price and can sometimes expose novel vulnerabilities. My research explores these vulnerabilities and the system-level effects of antibiotics to design treatments that take into account the physiological shortcomings associated to environmental conditions and use antibiotics to push bacterial functions past their tipping points.

In my research I develop mechanical models of the bacterial cell wall. I aim at theoretically deciphering the effect of drugs on the cell wall to understand the emergence of antimicrobial resistance.

My research is about transcription, a pathway governed by the enzyme RNA polymerase. In particular, I study the mechanism of RNA polymerase inhibition by specific antibiotics as well as the mechanism of resistance to such antibiotics at molecular level.

My research work focuses on deciphering the cell wall architecture of antimicrobial-resistant strains at the nanoscale using high-resolution atomic force microscopy.

I am currently developing methods for semi-automated image analysis on a number of Staphylococcus aureus strains, with a view to improve and speed up the time taken to acquire these data. We are interested in cell volume differences between strains, and changes within each, following antibiotic challenge. Additionally, the aim is to automate and quantify subcellular fluorescence localisation to determine any changes within septal vs. off-septal labelling.