Microbiology and Systems Biology focusing on computational microbiology

This programme of work focusses on using modelling and molecular simulations to characterise various aspects of bacteriophage-bacteria interactions.

Pathogenic bacteria remain an enormous problem for human, animal and plant welfare due to their resistance to most current antibiotics. The cell envelope that surrounds Gram-negative bacteria is composed of two membranes (the inner and outer) which are separated by an aqueous region known as the periplasm. Together these three regions provide the bacterium with a formidable defence against unwanted incoming molecules, including antibiotics. In recent years it has become apparent that bacteriophages, which are natural predators of bacteria have the potential to be co-opted for therapeutic purposes.

In this project, building upon recent work in structural biology and molecular modelling and dynamics of bacteriophage proteins in complex with their bacterial membrane receptors, we will address the following open questions:

1- How accessible are bacterial outer membrane receptors to the bacteriophage through the long O-antigen chains of lipopolysaccharide (LPS)?
2- How does the binding of the bacteriophage protein alter the conformational dynamics of the receptor protein?
3- What are the nature of the native LPS-bacteriophage proteins interactions? How do these vary across bacterial species?

Skills gained by the student:
Molecular modelling using traditional and AI-based methods.
Molecular simulations at > 2 levels of resolution.
Experience of running simulations on a range of High-Performance Computing architectures.
The ability to collaborate with structural biologists and to articulate

MRC strategic skill priorities:
Quantitative skills, particularly in analysis of simulation data, determining convergence of trajectories and identifying conserved molecular interactions.
Interdisciplinary skills in interpreting structural data and integrating with models to construct simulation systems