Objective Cardiovascular disease (CVD) is the main cause of death worldwide, and accounts for 40% of deaths within the EU. Monocytes are immune cells that are directly implicated in atherosclerosis, the leading cause of CVD. In both mouse and human there are two principle monocyte subsets, termed 'classical' and 'non-classical'. The classical monocyte subset is a key driver of atherosclerosis, whereas evidence suggests that the non-classical monocyte subset plays a protective role in disease. However, directly testing the role of non-classical (Ly6Clow) monocytes in disease has not been possible due to a lack of experimental models. In preliminary research Dr. Thomas used a novel multidisciplinary approach to generate mice that selectively lack Ly6Clow monocytes. This work identified a small region of the genome, termed an enhancer, that controls expression of the key transcription factor Nr4a1 in Ly6Clow monocytes. Deleting this enhancer produced a mouse that lacks Ly6Clow monocytes but is otherwise normal, unlike existing methods for Nr4a1 deletion. MONOCLE will exploit this novel mouse model to test the role of Ly6Clow monocytes in atherosclerosis, and to gain new insight into mechanisms regulating non-classical monocyte development. Thus, MONOCLE has the potential to reveal new molecular and cellular therapeutic targets in the battle against CVD. MONOCLE will also provide Dr. Thomas with new skills in in vivo CVD research, financial-management and project planning, forming the foundation for his role as a successful independent research group leader in Europe. The fellow will bring to the host institute a unique skill set enabling functional genomic and epigenetic analysis of in vivo cell populations, and access to a network of world-class researchers in epigenetics and monocyte biology. Hence, MONCOLE will bring new knowledge to Europe by facilitating cutting-edge, innovative research that directly addresses one of the largest societal health challenges. Fields of science medical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosismedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsgenomesnatural sciencesbiological sciencesgeneticsepigenetics Keywords Atherosclerosis Nr4a1 Nur77 non-classical monocyte CRISPR-Cas9 Enhancer Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator THE UNIVERSITY OF EDINBURGH Net EU contribution € 195 454,80 Address Old college, south bridge EH8 9YL Edinburgh United Kingdom See on map Region Scotland Eastern Scotland Edinburgh Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80