This project is one of a number that are in competition for funding from the ‘GW4 BioMed MRC Doctoral Training Partnership’ which is offering up to 18 studentships for entry in September 2020.
The DTP brings together the Universities of Bath, Bristol, Cardiff and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities.
Lead supervisor: Prof Samuel Sheppard, Department of Biology & Biochemistry, University of Bath
Co-supervisors: Dr Maisem Laabei (University of Bath), Prof Ruth Massey (University of Bristol) and Prof Alastair Hay (University of Bristol)
Bacteria live in complex communities with multiple species and strains competing with each other. Victories and defeats within these microbial wars are largely ignored unless they have a noticeable impact on the environment or the host, for example, when a disease causing strain emerges as a winner.
Typically, people think of pathogens being transmitted from person-to-person where they cause disease in the newly infected individual. However, most pathogens do not conform to an obligate closed-system infection model. Rather, they are symbionts that have followed a new ecological trajectory. In fact, many serious diseases (e.g., meningitis, pneumonia, blood/wound infections) are caused by bacteria that are common on the skin, mucous membranes, or in the guts of healthy humans. Because of this, bacterial species such as Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus and Staphylococcus epidermidis (all of which inhabit human epithelia commensally) are often described as ‘opportunist’ or ‘accidental’ pathogens.
The prevailing view, that infection is an accident of surgery (or other perturbations), means that the spread of so called opportunistic pathogens are far less well understood than some more infamous pathogens (eg. Mycobacterium tuberculosis), despite being (arguably) of greater clinical significance in many countries. However, pathogenicity is not an accident. In fact, the assumption that all strains in one niche (skin epithelium) are equally able to colonize a second niche (the blood), contradicts accepted evolutionary theories of niche transition and adaptation.
The student will gain an understanding of the evolution of the emergence of disease causing S. aureus, S. epidermidis, N. meningitidis, S. pneumoniae. Building on previous work from the Sheppard lab and across the supervisory team, the student will conduct an interdisciplinary program involving genomics, bioinformatics and laboratory microbiology. Using large bacterial strain (and genome) collections and novel bioinformatics approaches, including genome-wide association study approaches (GWAS) and machine learning linked to laboratory phenotypes, the candidate will identify genetic determinants of pathogenicity in commensal populations and identify high risk strains. Following on from the genomic analysis, laboratory competition experiments (in vitro and ex vivo - human epithelial tissue), involving knockout mutant strains, will investigate how competition in a fluctuating immune environment leads to the maintenance of potentially pathogenic strains and genes in the population. Specifically, how pre-adaptation to low-level immune response (minor epidermal damage) allows the co-existence of strains with adaptations that are potentially beneficial in invasive disease.
Broad expertise of the supervisory team will ensure training for the candidate in state-of-the-art practical and theoretical methodology. This program will improve understanding of why opportunistic bacteria become pathogens, when they are likely to do this and how we can interfere with their plastic responses to control virulence in a sustainable manner. Collaborations are in place within Public Health England and Wales, and commercial partners in Switzerland, who will test the relevance of the findings informing risk assessment, diagnosis, pre- and post- operative procedure, and targeted interventions providing immediate application of this study in a clinical context.
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project.
IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form: https://cardiff.onlinesurveys.ac.uk/gw4-biomed-mrc-doctoral-training-partnership-student-appl
You do NOT need to apply to the University of Bath at this stage – only those applicants who are successful in obtaining an offer of funding form the DTP will be required to submit an application to study at Bath.
More information on the application process may be found here: https://www.gw4biomed.ac.uk/doctoral-students/
APPLICATIONS CLOSE AT 17:00 ON 25 NOVEMBER 2019.