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  Deciphering host-oral microbiome interactions and mechanisms for prevention of dysbiosis and antimicrobial resistance


   Faculty of Medicine and Health

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  Dr T Do, Prof S Pavitt  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

Host-microbiome interactions play a key role in determining health and disease status. By deciphering the intricate signals within host and microbiome profiles we will advance knowledge for maintaining health and preventing dysbiosis. The significance of the microbiome on host health has led to the emergence of new therapeutic approaches focused on the prescribed manipulation of the host microbiome, either by decreasing harmful taxa or reinstating missing beneficial taxa and the functional roles they perform.

A rich and diverse microbiome is necessary for host organisms, as it contributes to the smooth development and functioning of important physiological processes. We will focus on the oral microbiota and its role maintaining the oral mucosal barrier. Reducing the portals for systemic translocation of organisms and disruption to systemic health from ensuing infections. This is particularly problematic in individuals whose immune system is compromised, highlighting the importance of understanding the underlying biological mechanisms at work. 

The oral cavity comprises microbes that attach to surfaces in communities called biofilms. These are highly regulated with complex interdependency of organisms that adapt to changes in the wider environment2. These biofilms are essential to health with multiple functions e.g. contributing to the maintenance of mucosa barrier that prevents invasion of disease-promoting species. Co-cultures allow for the study of cell–cell interactions that more closely mimic complex tissue structures (e.g. human cells–biofilm). Numerous studies are advancing understanding of the role of the microbiome as a therapeutic agent and its significance in human health.

We hypothesise that the oral microbiome signatures and associated host responses are distinct in health and in dysbiosis. Microbiome modulation strategies can prevent dysbiotic events and maintain health. 

Aims and Objectives

  1. To advance current understanding of the taxonomic and functional profiles of the oral microbiome in health and in dysbiosis, and screen for antimicrobial resistance genes harboured by the oral microbiome. 
  2. To construct and characterise co-cultured biofilms with oral epithelial cells. 
  3. To design in silico pipelines for oral health and prevention of dysbiosis modelling, using a deep learning approach. 

This BBSRC-funded iCASE studentship is a collaboration between Dr Do and Prof Pavitt at the University of Leeds, and GlaxoSmithKline Consumer Healthcare (GSK). 

You will be trained in human cell and oral biofilm co-culture, molecular methods of metagenomic and transcriptomic profiling, and bioinformatics, using state-of-the art facilities at the University of Leeds. Throughout the project, you will collaborate closely with highly experienced research scientists at both Leeds and GSK. As a BBRSC iCASE student, you will be expected to spend three months on secondment at GSK Oral Health Research and Development (R&D) facility in Weybridge.

The University of Leeds is committed to recruiting exceptional postgraduate researchers regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. Our recruitment process is built to ensure equal opportunity, and we thrive to provide inclusive research-led curriculum, to enable all our students to achieve their future study and career aspirations. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

How to apply

For more information about this project and how to apply please visit the University of Leeds website.

Biological Sciences (4) Mathematics (25) Medicine (26)

Funding Notes

The BBSRC iCASE PhD studentship is available for applicants who are eligible to pay academic fees at the UK fee rate. The studentship will attract an annual tax-free stipend of £15,285 for up to 4 years, subject to satisfactory progress and will cover the academic fee at the UK rate.

References

Do T. 2017. Insights into microbial ecosystems using a new computational approach. Oral Diseases. 23(7), pp. 817-819.
Kilian M, Chapple ILC, Hannig M, et al. The oral microbiome – an update for oral healthcare professionals. BDJ. 2016;221:657–666.
Cheng Z, Do T, Mankia K, Meade JL, Hunt L, Clerehugh V, Speirs A, Tugnait A, Emery P, Devine DA. Dysbiosis in the Oral Microbiomes of anti-CCP Positive Individuals at Risk of Developing Rheumatoid Arthritis. 2021 Feb;80(2):162-168. doi: 10.1136/annrheumdis-2020-216972.

Where will I study?