About the Project
We work on the mechanisms of lung injury, repair and fibrosis, with a particular focus on how monocytes and macrophages influence these processes. Our current focus is on how monocyte-derived macrophages contribute to lung fibrosis and we have also begun studies on how lung resident cells influence repair and regeneration. We use murine models, single cell genomics, mass and advanced flow cytometry to explore our questions.
The lung is a distinct organ in terms of regeneration and self-renewal. In the steady-state, cell turnover is low, but after injury, it possesses tremendous ability to regrow its epithelium - a whole new lung segment can regenerate after partial pneumonectomy. Yet, in end stage lung disease idiopathic pulmonary fibrosis (IPF), regeneration is rare or occurs abnormally. The project offered examines the role of tissue-resident immune cells (innate lymphoid cells, Tregs, resident alveolar macrophages) in maintaining steady-state quiescence and coordinating appropriate repair after injury of the alveolar epithelium. The work will focus on the use of improved bleomycin murine model to examine the in vivo changes in tissue resident immune cells in the lungs, its co-localisation with regenerating alveolar epithelium and alveolar progenitor cells during injury and regeneration/repair. Findings will be tested in the appropriate transgenic mice and human diseased lungs in collaboration
The group currently use these methods routinely to explore our scientific hypotheses: murine models of lung injury and repair, multi-colour flow cytometry, CYTOF, single cell genomics, immunohistochemistry, and standard qPCR, Western blots and tissue culture.
As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.
All MRC WIMM graduate students are encouraged to participate in the successful mentoring scheme of the Radcliffe Department of Medicine, which is the host department of the MRC WIMM. This mentoring scheme provides an additional possible channel for personal and professional development outside the regular supervisory framework.
Funding Notes
Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.
Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.
References
M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza. Cole SL, Dunning J, Kok WL, Benam KH, Benlahrech A, Repapi E, Martinez FO, Drumright L, Powell TJ, Bennett M, Elderfield R, Thomas C; MOSAIC investigators, Dong T, McCauley J, Liew FY, Taylor S, Zambon M, Barclay W, Cerundolo V, Openshaw PJ, McMichael AJ, Ho LP. JCI Insight. 2017;2(7):e91868.
Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza. Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ; MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJM. Nat Immunol. 2018;19(6):625-635
Epithelial-derived TGF-β1 acts as a pro-viral factor in the lung during influenza A infection. Denney L, Branchett W, Gregory LG, Oliver RA, Lloyd CM. Mucosal Immunol. 2018;11(2):523-535.
Pulmonary Epithelial Cell-Derived Cytokine TGF-β1 Is a Critical Cofactor for Enhanced Innate Lymphoid Cell Function. Denney L, Byrne AJ, Shea TJ, Buckley JS, Pease JE, Herledan GM, Walker SA, Gregory LG, Lloyd CM.Immunity. 2015;43(5):945-58.
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