About the Project
Our immune system must be ready to attack harmful pathogens that enter the body, but at the same time remain silent against harmless substances we come into contact with in everyday life. This is particularly important in the lung, where the immune system must ignore the abundance of innocuous antigens we inhale. The immune system in the lung is therefore tightly regulated to prevent inflammation and maintain health. However, the downside to this tight regulation is that it may suppress/limit protective responses to some pathogens, leading to harmful and sometimes fatal infection. It is therefore crucial that we understand the cells and pathways that limit inflammation in the lung when we are healthy so that these can be therapeutically targeted during infection to boost the immune response against the pathogen.
In collaboration with the Defence Science and Technology Laboratory (Dstl), we will focus on a recently discovered type of immune cell called innate lymphoid cells (ILCs), and how these control bacterial infection in the lung and other key organs. We will determine how different types of ILCs respond during infection, along with their functional importance in regulating the immune response and the mechanisms by which they promote regulation. Understanding ILC biology may help to identify treatments to promote beneficial functions during infection, predict how well people will fight infections, and help inform future vaccine strategies. Thus, together the work will highlight potential novel treatments for promoting beneficial immune responses against bacterial infection.
The PhD student will join the teams of Dr. Mark Travis and Dr. Matt Hepworth in the Manchester Collaborative Centre for Inflammation Research (MCCIR), a world-leading centre for immunology and inflammation research in the Faculty of Biology, Medicine and Health at the University of Manchester. Dr. Travis is an international leader on how cytokines control immunity during health and inflammation, with Dr. Hepworth being a world expert on how different types of ILC promote regulate immune responses. Work is in collaboration with colleagues at Dstl who are international experts on models of severe bacterial infection. Overall, the student will receive extensive multi-disciplinary training in immunology, bacteriology and in vivo models of disease in a world class research environment.
Mark Travis: http://www.mig.manchester.ac.uk/people/marktravis/
Matt Hepworth: http://www.mig.manchester.ac.uk/people/matthewhepworth/
Dstl: https://www.gov.uk/government/organisations/defence-science-and-technology-laboratory
This is a potential studentship to be funded via the MRC Doctoral Training Programme. Projects under this scheme are competitively funded; i.e. there are more projects advertised than available.
Funding Notes
Please make direct contact with the Principal Supervisor to arrange to discuss the project and submit an online application form as soon as possible. There is no set closing date; projects will be removed as soon as they are filled.
Applications are invited from UK/EU nationals. Candidates from outside of the UK must have resided in the UK for 3 years prior to commencing the PhD in order to be eligible to apply. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.
References
- 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 Immunology, 10:624-34.
- Worthington JJ, Kelly A, Smedley C, Bauché D, Campbell S, Marie JC, Travis MA (2015). Integrin αvβ8-mediated TGFβ activation by effector regulatory T-cells is essential for suppression of T-cell-mediated inflammation. Immunity, 42: 903-915.
- Hepworth MR, Fung TC, Masur SH, Kelsen JR, McConnell FM, Dubrot J, Withers DR, Hugues S, Farrar MA, Reith W, Eberl G, Baldassano RN, Laufer TM, Elson CO, Sonnenberg GF (2015). mmune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells. Science. 348: 1031-5
- Hepworth MR, Monticelli LA, Fung TC, Ziegler CG, Grunberg S, Sinha R, Mantegazza AR, Ma HL, Crawford A, Angelosanto JM, Wherry EJ, Koni PA, Bushman FD, Elson CO, Eberl G, Artis D, Sonnenberg GF (2013). Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature. 498: 113-7.
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