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(MRC DTP) The importance of 24h rhythms in the gut microbiome for immunity


Project Description

The gut microbiome is a collection of trillions of organisms. These bacteria and the metabolites they produce (through the breakdown of dietary components) play a critical role in the maintenance of immunity. Changes in the balance of the microbiome are associated with the development of autoimmune disorders, allergy and susceptibility to infection(1). The composition and function of the microbiome varies over the course of the 24h day. This is a consequence of timing of meals, the composition of the diet and the host’s internal 24h (circadian) clock. These daily rhythmic changes in the microbiome are important for maintaining circadian rhythms both locally, and within distal tissues such as the liver(2). We are now interested in exploring the importance of rhythms in the gut microbiome for maintenance of immune health. We have shown in our laboratory that tissue levels of short chain fatty acids (SCFAs) show strong day-night variation, and it is well established that these microbial metabolites are an important link between the microbiota and immune system.

The immune system operates on a 24h schedule(3). Processes important for maintaining immune homeostasis, such as trafficking of immune cells around the body, are under circadian control. Furthermore, the amplitude of a response to inflammatory insult varies over the course of 24h(4). Finally, often chronic inflammatory diseases (such as rheumatoid arthritis and asthma) show 24h variation in disease symptoms(5). All these rhythms are driven by cell intrinsic clocks, which are entrained by extrinsic cues such as hormones or feeding-derived signals. We propose that circadian rhythmicity in immunity may be driven by the rhythmic microbiome.

This project will utilise a range of approaches to address the aims including germ free and transgenic mice, 16S sequencing of the gut microbiome, metabolomics, flow cytometry and fluorescence assisted cell sorting to temporally track gene transcripts in immune cells. You will join a dynamic team of researchers with an excellent track record.

https://www.bmh.manchester.ac.uk/research/biological-timing/

https://www.bmh.manchester.ac.uk/research/domains/infection-immunity-inflammation-repair/immunology/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

(1)Honda and Littman (2016) The microbiota in adaptive homeostasis and disease. Nature 535:75-84. (2) Thaiss et al. (2016) Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167:1495-1510. (3) Scheiermann et al. (2018) Clocking in to immunity. Nat Rev Immunol 18:423-427. (4) Gibbs et al. (2014) An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action. Nat Med 20:919. (5) Hand et al. (2016) The circadian clock regulates inflammatory arthritis. FASEB J 30:3759

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