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Discovering how polycomb domains form and function in gene regulation

Objective

Polycomb group chromatin modifying systems are essential for normal gene regulation and development, and alterations in their activity are a hallmark of a broad range of cancers. Although the chromatin modifications placed by the two central polycomb protein complexes (PRC1 and PRC2) are well-characterized, how this fascinating system selects its target sites in vivo, and then forms polycomb chromatin domains that are repressive to transcription remains enigmatic. This constitutes the major conceptual gap in our understanding of this essential gene regulatory system. We recently discovered a new pathway that is sufficient in model systems to initiate polycomb chromatin domain formation. Building on this discovery, an ambitious high-risk/high-reward yet hypothesis-driven multidisciplinary approach integrating biochemical, molecular, genomic, and single-cell analyses will be exploited to discover the fundamental principles that underpin polycomb domain formation and subsequently transcriptional repression. Specifically, the three aims of the research programme are to: (i) Discover how the KDM2B/PRC1 complex initiates polycomb domain formation, (ii) Discover how polycomb target sites are selected and polycomb domains formed during normal cell lineage commitment, and (iii) Discover how polycomb domains regulate gene expression. Going well beyond the state-of-the-art, our innovative approaches will lead to major new breakthroughs closing the conceptual gap that currently limits our understanding of how polycomb complexes regulate gene expression, an essential first step towards the possibility of devising strategies for therapeutic intervention in human cancers and other diseases where these systems are perturbed. Furthermore, support from the ERC in tackling these important problems will allow me to recruit the talented individuals necessary to achieve our objectives and consolidate my position as an emerging leader in the field.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-COG - Consolidator Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2015-CoG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 999 416,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 999 416,00

Beneficiaries (1)

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