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Biophysical modelling of bacterial cell wall architectures

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Bacterial cell walls are examples of self-assembled composite structures that are formed out of equilibrium. In recent times the text book view of bacterial cell wall has been modified as a result of high resolution imaging studies[1, 2]. The major and essential structural constituent of the bacterial cell wall is peptidoglycan (PG), whose biosynthesis is the target for antibiotics such as penicillin and vancomycin. Despite its healthcare importance the molecular architecture of PG, the processes which control its homeostasis, and its many functions are poorly understood.

The current view is that mature bacterial cell walls are made of PG strands which are crosslinked to each other by peptides to form a network structure having appropriate mechanical resilience against internal turgor pressure and changes in external environment. The cell wall however allows ingress and egress of molecules such as nutrients and long chain macromolecules rendering the view that it has a highly dynamic and complex architecture.

How does such a complex dynamic structure help maintain the cells integrity while simultaneously allowing for high throughput? The main aim of this project is to explain this puzzle taking recourse to computer simulations and analytical theory by gleaning insights from the physics of polymer composite materials.

Objectives:
We will develop a quantitative mechanistic understanding of:
i. the role of cell wall architecture in protein/macromolecule ingress and egress.
ii. the mechanical properties of the cell wall and how it resists innate immune attack

Theoretical approach:
Using a combination of coarse-grained molecular dynamics simulations and a combination of mean field and classical field theories we will model translocation of small molecules through composite materials having dynamic architecture incorporating cargo-channel interactions. We will also develop a coarse-grained model of the bacterial cell wall and study its mechanical properties against deformation. The theoretical studies will be closely aligned with experimental work in the labs of Profs. Jamie K. Hobbs and Simon Foster.


Science Graduate School:
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School – a community of postgraduate researchers working across biology, chemistry, physics, mathematics and psychology. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

UK and EU applicants who meet the UK residency requirements are eligible for EPSRC studentships.

If you submit your application after the 31 March 2019, you will be considered for any remaining funding, but please note all of our funding may be allocated in the first round.

References

[1] Turner, R.D. et al. (2010) Nature Communications doi: 10.1038/ncomms1025
[2] Lund, V.A. et al. (2018) eLife doi: 10.7554/eLife.32057.

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