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PhD Studentship: Microbial and Host Interactions in the Gut Microbiome

University of Birmingham - School of Biosciences

Qualification Type: PhD
Location: Birmingham
Funding for: UK Students, EU Students, International Students
Funding amount: BBSRC-funded
Hours: Full Time
Placed On: 2nd November 2021
Closes: 9th January 2022

Gut microbiome and health: We have begun to discover the multitude of ways in which microbes affect our health. Microbial therapies are undergoing extensive experimentation and human trials (including faecal microbial transplantation and probiotics) and the use of microbial therapies is changing clinical practice in some disease settings, such as antibiotic-refractory C. difficile infection.

Gaps in our understanding: An important issue with sequencing DNA extracted from poo is that the spatial structure in which the various microbes are self-organized in the gut community, facilitating local interactions between neighbours, is completely destroyed. Likewise, many mathematical models to date ignore spatial structure by effectively modelling the gut as a well-mixed system. We know from our work and other studies how important spatial structure is and also that mathematical models can predict how competitive and cooperative interactions generate certain spatial structures. The ability to predict and model such ecologies will be highly beneficial as more and more bacteria are identified as beneficial (potential probiotics) and as we need to understand the competition between ‘good’ and ‘bad’ bacteria. What is needed is model-aided design of synthetic multispecies probiotics where different members work together to form a stable community.

Approach: Issues with current research can only be overcome by integrating laboratory experiments with animal and clinical studies by using mathematical models as the glue between them. Mathematical models can take data from one system as input to predict dynamics in another system, which can then be contrasted with data from that system. Many challenges arise from the complexity of the gut. Models, mathematical and laboratory, help by simplifying this system, but one needs to check the simplifications are not caricatures of the system. eGut. We have been developing an agent-based model to simulate the gut microbial community called eGUT for electronic gut. This work has been funded by NC3Rs and has progressed to a stage where the model can be applied to understand and predict a variety of interactions between microbes and microbes and the host mucosa. Project aim and objectives.

The aim of this project is to study the competition of pathogens with commensal or probiotic bacteria in the gut environment using a combination of mathematical and laboratory models of the gut and time permitting animal or human study data from collaborators. As the mathematical model is challenged with experimental data, it will be improved and validated iteratively. Additionally, through a recent clinical trial examining the efficacy of faecal transplant in treating inflammatory bowel disease, a number of key bacteria that could act therapeutically have been identified; utilising this model to predict how we could best deliver these bacteria (within probiotic formulations) would be clinically useful and will be utilised in this project. Methods and skills. The project enables learning a wide range of skills and cross disciplinary working, from computer programming, modelling, data analysis and statistical inference to culturing bacteria and running laboratory models of the gut. Analysis could include metabolomics, qPCR, sequencing or flow cytometry.

This project is part of the Midlands Integrative Biosciences Training Partnership 3 (MIBTP2020). This is a BBSRC-funded doctoral training partnership between the University of Warwick, University of Birmingham, University of Leicester, Aston University and Harper Adams University recruiting students for four-year studentships starting in Oct 2022.

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