About the Project
This project will address the key question of how the lung environment modulates the ability of DCs to activate and direct Type 2 inflammation. The focus of the project will be the helminth Schistosoma mansoni, the immune response to which is strongly Type 2 biased and intimately involved in the pathology that accompanies infection. Schistosomiasis is second only to malaria in terms of the number of deaths caused annually by a parasitic disease. However, the key cellular and molecular networks that comprise immunity, inflammation and tissue repair against invading larval schistosomes are still unclear, particularly in the lung. Central to the project will be use of murine models to delineate the role of the lung environment (including surfactant and mucus) in controlling pulmonary DC activation and function in response to lung stage S. mansoni, with complementary work using allergens such as house dust mite.
This project will reveal exciting new information about the core mechanisms involved in coordination of pulmonary Type 2 inflammation by DCs, which may help future design of innovative therapies and vaccines for both helminth infection and allergies.
Training/techniques to be provided:
The successful candidate will receive training in a range of cutting-edge immunological techniques used in the MacDonald and Allen labs, including multi-parameter flow cytometry and mass cytometry (CyTOF), as well as gaining significant experience in in vivo models of inflammation, infection and allergy. Additional approaches such as refined isolation of immune cells from tissues, quantitative PCR, confocal microscopy and ELISA will also be used to define the activation and function of pulmonary DCs ex vivo and in vitro.
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in Immunology or a closely related area/subject. Candidates with experience in cellular immunology or with an interest in mechanistic understanding of inflammation during helminth infection and/or allergic disease are encouraged to apply.
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
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.
Lauren M. Webb, Rachel J. Lundie, Jessica G. Borger, Sheila L. Brown, Lisa M. Connor, Adam N. R. Cartwright, Annette M. Dougall, Ruud H.P. Wilbers, Peter C. Cook, Lucy H. Jackson-Jones, Alexander T. Phythian-Adams, Cecilia Johansson, Daniel M. Davis, Benjamin G. Dewals, Franca Ronchese and Andrew S. MacDonald. A central role for Type I IFN in Th2 response induction by dendritic cells. 2017. EMBO Journal. 36:2404-2418
Rachel J. Lundie, Lauren M. Webb, Angela K. Marley, Alexander T. Phythian-Adams, Peter C. Cook, Lucy H. Jones, Sheila Brown, Rick M. Maizels, Louis Boon, Meredith O’Keefe and Andrew S. MacDonald. A central role for hepatic conventional dendritic cells in supporting Th2 responses during helminth infection. 2016. Immunology and Cell Biology. 94:400-410
Peter C. Cook, Heather Owen…, Adrian Bird and Andrew S. MacDonald. A dominant role for the methyl-CpG binding domain protein Mbd2 in controlling Th2 induction by dendritic cells. 2015. Nature Communications. 6: 6920
Carlos Minutti, Lucy Jackson-Jones…. Cristina Casals and Judith E. Allen. Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver. 2017. Science 356, pp. 1076-1080
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