A novel enhancer deletion strategy to determine non-classical monocyte function in atherosclerosis

Información del proyecto

MONOCLE

Identificador del acuerdo de subvención: 705771

DOI

10.3030/705771

Proyecto finalizado el 11 Enero 2017

Fecha de la firma de la CE 3 Marzo 2016

Fecha de inicio 1 Enero 2017

Fecha de finalización 31 Diciembre 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 195 454,80

Aportación de la UE

€ 195 454,80

Coordinado por

THE UNIVERSITY OF EDINBURGH
United Kingdom

Objetivo

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.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › medicina clínica › cardiología › enfermedad cardiovascular › arteriosclerosis
• ciencias médicas y de la salud › medicina básica › inmunología
• ciencias naturales › ciencias biológicas › genética › genoma
• ciencias naturales › ciencias biológicas › genética › epigenética

Palabras clave

• Atherosclerosis
• Nr4a1
• Nur77
• non-classical monocyte
• CRISPR-Cas9
• Enhancer

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

THE UNIVERSITY OF EDINBURGH

• Aportación neta de la UEn: € 195 454,80
• Dirección: OLD COLLEGE, SOUTH BRIDGE ; EH8 9YL Edinburgh ; Reino Unido
• Región: Scotland › Eastern Scotland › Edinburgh
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 195 454,80