Controlling monocyte and macrophage function in cardiovascular inflammation and regeneration
Monocytes and macrophages are key mediators of injury, repair and regeneration in cardiovascular diseases and they are widely regarded as potential therapeutic targets. We have been using sequencing techniques to understand monocyte / macrophage function in (1) acute myocardial infarction, (2) atherosclerosis and (3) heart regeneration. Most recently we have opened a new area for research in this area by showing that exosomes derived from endothelial cells (and enriched for specific miRNA) control the transcriptional activation and mobilisation of monocytes. We are also interested in how macrophage function is altered in hyperglycemia / type 2 diabetes and in the phenomena around “metabolic memory” as part of the Novo Nordisk Foundation TriPartite Immuno-metabolism Consortium [Oxford-Copenhagen-Karolinska, PI Choudhury]
This project provides an opportunity for a talented computational biologist / programmer to work with us to understand and integrate existing and emerging complex “-omics” data sets in the field innate immunity / immuno-metabolic function. These span exosomal miRNA; monocyte transcriptomics and patterns of chromatic modification in experimental models and human-derived tissues. The challenges include (1) identification of upstream functional modulators (e.g. from miRNA; metabolomics data sets); (2) imputing down stream targets (e.g. functionally important pathways identified through RNAseq and proteomics approaches and (3) determining specific potentialities and susceptibilities based on chromatin modification. We commonly obtain equivalent samples from mice and humans and corroborate our observations through cross-species comparisons.
A D.Phil candidate working on this project would be jointly supervised by Prof Robin Choudhury (RDM; vascular biology; innate immune function) and Dr David Sims (Director of the MRC Computational Genomics Analysis and Training programme [CGAT]) and will be based in the Weatherall Institute of Molecular Medicine at CGAT.
As well as training specific to the project detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.
Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, public engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.
The department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.
Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans.Ruparelia N. et al, (2015), Eur Heart J, 36, 1923 – 1934. PMID: 25982896
Akbar N. et al, (2017), JCI Insight, 2017 doi: 10.1172/jci.insight.93344 2PMID: 28878126