(MRC DTP) Microbiome - circadian clock interactions: impact on immunity

The circadian clock is an internal timing mechanism which allows organisms to align their physiology with the daily 24h environment. This allows animals to anticipate daily changes in the environment (e.g. lighting and food availability) and adapt their physiology accordingly, thus enhancing survival. This internal body clock regulates many different physiological processes including the sleep-wake cycle, hormone secretion, metabolism and immunity. Our group focuses on understanding how the circadian clock regulates the immune system with the aim of understanding how responses to infection and inflammation vary across the 24h day.

Anatomically, there is a central clock, which resides within a region of the brain called the suprachiasmatic nucleus (SCN) where it receives light input from the eyes. The SCN entrains peripheral clocks located within multiple different cells, tissues and organs around the body. In recent years, it has been established that many immune cells possess clocks, including macrophages(1) and dendritic cells. Additionally, resident immune cells within the lung, joints and gut(2) possess the clockwork machinery and show variation in function over 24h. These peripheral clocks are entrained by the central brain clock, but are also sensitive to other cues, such as feeding.

Recently it has been demonstrated that the gut microbiome (microorganisms dwelling within the intestines) shows circadian variation, with changes in both composition and function over the course of a day(3). Critically, the microbiome (and microbiome derived metabolites) plays a key role in regulating immunity(4 and 5). Changes in the balance of the microbiome are associated with the development of autoimmune disorders, allergy and susceptibility to infection. Intriguingly, depletion of the gut microbiome affects circadian rhythms not only in the gut, but also in distal tissue, such as the liver(3). We are now interested in understanding how clocks within the gut influence daily changes in the microbiome and also vice versa, how changes in the microbiome affect rhythmicity in immune cells resident within the gut and elsewhere.

You will join a dynamic team of researchers with an excellent track record. The host laboratory is equipped with cutting edge facilities to carry out research into circadian control of immunity. The project will utilise a range of interdisciplinary approaches to address the aims including: specialised in vivo skills embracing germ free and transgenic mice, 16S sequencing of the gut microbiome and downstream bioinformatics, and fluorescence assisted cell sorting to temporally track gene transcripts in immune cells.

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.