Commensal bacteria present in the gastrointestinal tract provide beneficial roles for the host, such as supporting nutrient metabolism. In order to peacefully co-exist with the intestinal microflora the immune system has evolved multiple mechanisms through which it suppresses inflammatory immune responses against these mutualistic microorganisms, which together generate a tolerogenic environment. A breakdown in this tolerance can result in the onset of chronic inflammatory disorders such as Inflammatory Bowel Disease (and colon cancer), hepatitis, and rheumatoid arthritis.
Innate lymphoid cells (ILCs) play key roles in mediating intestinal immune homeostasis and maintaining healthy host-commensal bacteria interactions via the production of cytokines, interactions with other tissue-resident immune cell populations and the orchestration of local immune responses (reviewed in Sonnenberg and Hepworth, Nature Reviews Immunology 2019). In particular, recent studies have demonstrated that group 3 innate lymphoid cells (ILC3) are able to prevent intestinal inflammation by controlling the activation of commensal bacteria-specific inflammatory T cells in an antigen-specific manner (Hepworth et al Nature 2013, Science 2015). Moreover, we recently demonstrate that ILC3 also regulate secretory Immunoglobulin (Ig)A production in order to control commensal bacterial colonization within the gut (Melo-Gonzalez et al, J Exp Med 2019).
This project will investigate i) how ILCs interact with intestinal immune cells to regulate responses to commensal bacteria ii) which bacterial species preferentially drive intestinal inflammation following disruption of ILC regulatory function(s) and iii) the specificity of ILC-regulation of inflammatory responses.
The project will utilize a range of approaches including the use of animal models, immunological techniques (flow cytometry, ELISA), molecular biology (PCR, sequencing) and microbiological methods to investigate interactions between the host immune system and the commensal microbiota in the context of health and disease. The student will my join my laboratory located within the world-class Faculty of Biology, Medicine and Health (FBMH) and Lydia Becker Institute of Immunology and Inflammation at the University of Manchester and will have access to a wide range of facilities and expertise across the faculty.
Training/techniques to be provided:
- In vivo models of disease and immune function
- Basic Immunological techniques (Flow Cytometry, ELISA)
- Basic microbiological techniques (16S PCR, culturing and infections with bacterial species, germ free mice)
- Basic molecular biology techniques (RT-PCR, potential for RNA sequencing and/or genomics approaches)
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous laboratory experience, particularly in cell culture and molecular biology, are particularly encouraged to apply.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Genetics
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk