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Biogenesis of the Clostridium difficile cell surface

Department of Molecular Biology and Biotechnology

Dr R Fagan Applications accepted all year round Self-Funded PhD Students Only

About the Project

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in our hospitals. Infection normally follows disruption of the gut normal flora by broad-spectrum antibiotic treatment. Following disruption of the microbiota C. difficile colonises the gut and begins uncontrolled proliferation. The C. difficile cell surface is completely covered by a proteinaceous surface layer (S-layer) that mediates interactions between the pathogen and its host (Fagan and Fairweather, 2014). Biogenesis of this S-layer is a complex multistep process that begins with secretion of protein precursors via a dedicated accessory Sec system (Fagan and Fairweather, 2011), and is a promising target for the development of novel antimicrobials. The purpose of this project is to characterise key proteins in the S-layer secretion system. The project will involve the use of classic molecular microbiology and biochemical techniques, including genetic manipulation of an anaerobic pathogen, and analysis of protein secretion.

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 to learn more.

Funding Notes

Entry requirements:
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD position, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.


Fagan, R. P. and N. F. Fairweather (2014) Biogenesis and functions of bacterial S-layers. Nature Rev. Micro. 12:211-222

Fagan, R. P. and N. F. Fairweather (2011) Clostridium difficile has two parallel and essential Sec secretion systems. J. Biol. Chem. 286(31):27483-27493
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