Elucidating the role of Arid1a in adult liver

Project Information

EPILIPRO

Grant agreement ID: 702585

DOI 10.3030/702585

Project closed

EC signature date 17 March 2016

Start date 1 May 2016

End date 30 April 2018

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost € 183 454,80

EU contribution € 183 454,80

Coordinated by

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
United Kingdom

Objective

Liver cancer is the fifth most common malignancy in men and the eighth in women worldwide. Of note, liver cancer is tightly associated with tissue damage due to the high metabolic and drug detoxification activity of the liver. Increasing evidence demonstrates that toxic agents induce the activation of a resident ductal-progenitor population capable of regenerating the tissue. Therefore, understanding molecular mechanisms governing liver progenitor cells is essential for preventing tumour initiation and progression.
The aim of this proposal is elucidating the role of Arid1A (the DNA-binding subunit of the nucleosome-remodelling complex SWI/SNF) in adult liver progenitors by using novel 3D-organoid cultures, which allows long-term expansion of adult ductal-progenitors derived from the healthy liver. Moreover, genome-wide analysis and in vivo approaches will be implemented for accomplishing the goals of the project. Supporting a crucial role for Arid1a in liver progenitors, Arid1a expression is high in organoid cultures and is up-regulated in the adult liver upon damage as compared to the healthy liver. Importantly, Arid1a and other SWI/SNF subunits are mutated in liver cancer, suggesting that Arid1a and SWI/SNF exert a tumour suppression function. In line with this, our preliminary results indicate that depletion of Arid1a and SWI/SNF components increases organoid formation efficiency.
Overall, this research plan will shed light on the function of Arid1a and the SWI/SNF nucleosome-remodelling complex in adult liver progenitors and mouse liver regeneration, providing novel hints into their role in carcinogenesis.

Fields of science

• medical and health sciences › clinical medicine › oncology › liver cancer
• natural sciences › biological sciences › developmental biology
• medical and health sciences › medical biotechnology › cells technologies › stem cells
• medical and health sciences › clinical medicine › hepatology
• medical and health sciences › health sciences › nutrition › obesity

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

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

• Net EU contribution: € 183 454,80
• Address: TRINITY LANE THE OLD SCHOOLS ; CB2 1TN Cambridge ; United Kingdom
• Region: East of England › East Anglia › Cambridgeshire CC
• Activity type: Higher or Secondary Education Establishments
• Total cost: € 183 454,80