Funded BBSRC-GSK iCASE project:
deadline 27 February 2022

About the project

An exciting opportunity has arisen to join two vibrant interdisciplinary research groups within the University of Sheffield, crossing the Faculties of Medicine, Dentistry and Health as well as the Faculty of Engineering, and in partnership with global healthcare company, GSK.

Professor Graham Stafford has a multidisciplinary group focussing on a range of applied and fundamental microbiology research (Stafford Research Group) while Dr Jags Pandhal is an expert in proteomics and bioengineering (Pandhal Research Group). This means you will join an interdisciplinary team and receive a broad training that will also include knowledge of commercialisation of research.

A healthy oral microbiome is essential to maintaining oral and systemic health. Oral diseases cost the NHS billions of pounds while the oral healthcare market is also worth billions. However understanding how oral products affect the composition and function of the oral microbiota is weak.

Our overarching aim is to improve understanding of the responses of the human oral microbiome to active antimicrobial compounds in commonly used oral mouthwashes including Chlorhexidine. The use of these may also promote Antimicrobial Resistance (AMR). Our approach will use a novel metaproteomic approach to ‘take the pulse’ of oral microbiome cultures in parallel with microbiome classification (16S) via nanopore sequencing and biochemical virulence assays of in vitro oral microbiome communities.

It is essential that scientists start to examine function of bacterial communities rather than reductionist single species projects. The human microbiome, with the oral cavity being a good example, is responsible for maintaining health, with disruptions (dysbiosis) being linked to many conditions- e.g. IBD, Crohns, Periodontitis and caries.

While many studies monitor the microbiome, they usually simply catalogue species (16S studies) or potential function (metagenome) rather than actually looking at protein expression in response to perturbations. Our project will examine dynamic responses to oral active compounds and uncover mechanisms that will enable reconstruction of microbial processes and metabolic pathways that are central to the functioning of the oral ecosystem.

Our project will focus initially on Chlorehexidine (CHX) plus a novel active under development at GSK (placement work)- that you will also aid to identify during work with GSK at their base in the UK, examining factors important in product development. CHX is a common antimicrobial in daily mouthwashes, with continued usage altering the microbiome and affecting blood-pressure modifying compounds (e.g. nitrite). In addition, CHX use can induce resistance to antibiotics in some bacteria.

The data and techniques developed will allow improvement and design of future actives by GSK-consumer healthcare and improve our understanding of the human microbiome.

Entry Requirements

Students should have, or be expecting to recieve at least an upper second class honours degree, or equivalent. The interdisciplinary nature of this programme means that we welcome applications from students with a variety of backgrounds.

If you have a degree in any biological, chemical, or physical science, or if you have a mathematical background and are interested in using your skills in addressing biological questions.

Funding

This studentship is part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology and by GSK Consumer Healthcare Innovation research. Appointed candidates will be funded for 4 years, including:

• Tax-free annual UKRI stipend (£15,609 for 2021/22 starts) PLUS an iCASE top-up to stipend of £3,000.

• UK tuition fees (Around £4,500 per year)

• Research Training and Support Grant (RTSG) PLUS funding from iCASE partner for consumables.

• Placement funding from the industry partner - 3 months over 4 years.

We are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants.