Kennedy Trust Prize Studentships
Transcriptional and metabolic adaptation of myeloid cells to inflammatory environment
Chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, diabetes etc are increasing in prevalence all over the world. Despite progress in understanding how they develop and what components of the immune system may be involved, much remains unknown (1).
We have previously shown that myeloid cells, such as monocytes, macrophages and neutrophils, are important in inflammatory diseases (2). Our new data suggest that inflammatory monocytes adapt their immune and metabolic functions to the tissue microenvironment and release chemokines and bioactive signalling lipids that drive neutrophil accumulation in the tissue during sterile inflammation. To better understand the spatiotemporal relationship between myeloid cells entering the tissue during sterile inflammation and the molecular mechanisms involved, we will combine transcriptional and lipidomic profiling of inflammatory monocytes in the tissue (2) with advanced imaging (3).
Our analysis of myeloid cell populations during the course of sterile inflammation will reveal signalling cascades that control different aspects of the inflammatory response. These studies will also lead to new insights into the interactions of bioactive lipids with proteins of the inflammatory system, which will help to define novel combinatorial drug/diet treatments designed to correct specific elements of the interactions.
The Kennedy Institute is a world-renowned research centre and is housed in a brand new state-of-the-art research facility. The project will utilise a range of functional genomic (RNA-Seq, ATAC-Seq, ChIP-Seq) and lipidomic (LC-MS/MS) approaches, imaging (immunofluorescence on tissue sections) and immunological (cell isolation, tissue culture, FACS, CyTOF) techniques. We will be based on recently developed novel in vivo models. Subject-specific training will be received through the groups' weekly meetings. A core curriculum of 20 lectures will be taken in the first term of year 1 to provide a solid foundation in immunology, inflammation and data analysis. Students will attend weekly departmental meetings and will be expected to attend seminars within the department and those relevant in the wider University. Students will also attend external scientific conferences where they will be expected to present the research findings.
- Udalova IA, Mantovani A, Feldmann M. Macrophage heterogeneity in the context of rheumatoid arthritis. Nature Reviews Rheumatology. 2016 Aug;12(8):472-85.
- Weiss M, Byrne AJ, Blazek K, Saliba DG, Pease JD, Perocheau D, Feldmann M, Udalova IA. IRF5 controls both acute and chronic inflammation. PNAS. 2015 Sep 1;112(35):11001-6.
- Arnon TI, Horton BM, Grigorova IL and Cyster JG. Visualization of splenic marginal zone B cell shuttling and follicular B cell egress. (2013) Nature 493(7434):684-8.