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  • Project No: #MRC1
  • Intake: 2020 MRC
  • Monaco

Project overview

Macrophages have a key role in health and disease, by supporting organ function and immune responses to damage and disease (1). In homeostasis, ontogeny and organ-specific signals influence the phenotype and function of macrophages by activation of specific transcription factors. Disruption of homeostasis due to inflammation, infection or disease results in a drastically altered tissue micro-environment with the influx of newly recruited monocytes and macrophages and inflammatory substances. The macrophage phenotype under non-homeostatic conditions is reshaped by integration of maturation, polarisation, activation and deactivation events via growth factors and cytokines, inducing a myriad of activation states. 

The study of the functions of vascular macrophages has so far been neglected and is a current area of exciting discovery. Atherosclerosis is an exemplar of how mononuclear phagocytes are directly implicated in disease pathogenesis. We have recently applied single cell technologies to the identification of both resident and inflammatory vascular macrophages in atherosclerosis (2). We have also shown how modulating macrophage behaviour affects atherogenesis and plaque complications (3). 

This project aims to investigate the biology and molecular regulation of vascular macrophages and how they function in health and disease. Using single cell technologies combined with genetic deletion and fate mapping, and functional genomics we will define the transcriptional and functional profile of vascular macrophages. The results will contribute to our understanding of the contributions of vascular macrophages to cardiovascular health and disease and it will explore the fundamental molecular mechanisms regulating tissue resident macrophage programming

Relevant Publications

  1. Gordon et al. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunological Reviews 2014 https://doi.org/10.1111/imr.12223 
  2. Cole et al. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity. Cardiovasc Res. 2018 Aug 1;114(10):1360-1371. doi: 10.1093/cvr/cvy109.
  3. Seneviratne et al. Interferon Regulatory Factor 5 Controls Necrotic Core Formation in Atherosclerotic Lesions by Impairing Efferocytosis.Circulation. 2017 Sep 19;136(12):1140-1154. doi: 10.1161/CIRCULATIONAHA.117.027844. 

 Themes: ImmunologyCardiovascular diseaseMolecular, Cell and Systems Biology

Training

The Kennedy Institute is a world-renowned research centre, housed in a brand new, state-of-the-art facility at the University of Oxford. The Kennedy Institute provides access to outstanding core facilitates including advanced imaging equipment, multiparameter cell sorting and analysis, mass cytometry, deep sequencing, a full histology core and bioinformatics infrastructure.

Training will be provided in techniques including models of atherosclerosis and state-of-the-art single cell platforms (e.g. mass cytometry (CyTOF)), as well as a range of immunology, cellular and molecular biology techniques, and single cell genomics. Mass cytometry is a significant innovation that takes advantage of the measurement resolution of Inductively Coupled Plasma (ICP) mass spectrometry and applies it to single-cell analysis. The cytometry time of flight (CyTOF®) “mass cytometer” provides for the first time, the ability to simultaneously quantitate at least 40 intracellular and extracellular parameters in individual cells. 

A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology and data analysis.

Students will attend weekly seminars within the department and those relevant in the wider University. 

Students will be expected to present data regularly to the department, the Cardiovascular Inflammation Group and to attend external conferences to present their research globally. Students will also have the opportunity to work closely with the Genomics of Inflammation Group.

How to Apply

The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisor(s) or the Directors of Graduate Studies who will be able to advise you of the essential requirements. 

Interested applicants should have or expect to obtain a first or upper second class BSc degree or equivalent, and will also need to provide evidence of English language competence. The University requires candidates to formally apply online and for their referees to submit online references via the online application system. 

The application guide and form is found online and the DPhil or MSc by research will commence in October 2020. 

When completing the online application, please read the University Guide: https://www.ox.ac.uk/admissions/graduate/applying-to-oxford/application-guide?wssl=1

Further information

Contact: Professor Claudia Monaco, Kennedy Institute of Rheumatology, University of Oxford