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Determining how immune responses are regulated at mucosal surfaces


Project Description

The immune system must be primed to quickly respond to infection, but must also be tightly regulated so it ignores harmless substances and our own tissues. A breakdown in immune system regulation can result in illnesses such as allergy (when our immune system attacks harmless substances) and autoimmune diseases such as inflammatory bowel disease, diabetes and arthritis (where the immune system attacks our own body). Therefore understanding the pathways and mechanisms that keep the immune system in a resting state at times of health are vital in understanding what goes wrong to cause allergy and autoimmune disease.

This balance is especially crucial at so-called ‘mucosal surfaces’, like those found in the lung and the gut. These surfaces have major exposure to the environment, and also have a so-called ‘microbiota’ made up of micro-organisms that help keep the body healthy, but can be attacked by the immune system.

This project will study how cells of the immune system communicate with one another in the lung and gut to fight infection and prevent allergy and autoimmune disease. Specifically, the project will focus on how an important molecule called TGF-beta affects immune responses. Additionally, we are interested in how the physical mucus barrier in the lung and gut can communicate with the immune system to regulate its function.

The project will utilise a variety of different techniques including animal models, human samples, molecular biology and cell culture models to study how the immune system is regulated in the lung and gut.

The student will join my laboratory located within the world-class Lydia Becker Institute of Immunology and Inflammation, located within the Faculty of Biology, Medicine and Health Sciences at the University of Manchester, and will have access to a wide-range of expertise and facilities present within the faculty.

Training/techniques to be provided:
The student will learn a variety of immunological and cell biology techniques, including how to isolate immune cells from tissues, analysis of cells by multi-colour flow cytometry, mouse models of the immune system, cell culture and molecular analyses such as qPCR and RNA-sequencing.

Entry Requirements:
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 research experience are encouraged to apply, especially those with some experience in immunological techniques.

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

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy 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

Casulli J, Fife ME, Houston SA, Rossi S, Dow J, Williamson ED, Clark GC, Hussell T, D'Elia RV, Travis MA (2019).
CD200R deletion promotes a neutrophil niche for Francisella tularensis and increases infectious burden and mortality. Nat Commun. 10:2121.

Kelly A, Gunaltay S, McEntee CP, Shuttleworth EE, Smedley C, Houston SA, Fenton TM, Levison S, Mann ER, Travis MA (2018). Human monocytes and macrophages regulate immune tolerance via integrin αvβ8-mediated TGFβ activation. J Exp Med., 215:2725-2736.

Melo-Gonzalez F, Fenton TM, Forss C, Smedley C, Goenka A, MacDonald AS, Thornton DJ, Travis MA (2018). Intestinal mucin activates human dendritic cells and IL-8 production in a glycan-specific manner (2018). J Biol Chem. 293:8543-8553.

Fenton TM, Kelly A, Shuttleworth EE, Smedley C, Atakilit A, Powrie F, Campbell S, Nishimura SL, Sheppard D, Levison S, Worthington JJ, Lehtinen MJ, Travis MA (2017). Inflammatory cues enhance TGFβ activation by distinct subsets of human intestinal dendritic cells via integrin αvβ8. Mucosal Immunol. 10:624-634.

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