Project description
Exploring the epigenetics of unique genome regulation mechanisms
DNA methylation plays a key role in controlling gene expression and is essential for normal development and functioning of cells. This mechanism is often significantly altered in malignant cancers. Funded by the European Research Council, the CancerEpigenome project suggests that these alterations closely mirror patterns that emerge in the early placenta. Researchers deem that both the cancer and the placental epigenome reflect a switch-like programming event that can be triggered without genetic mutation. To prove this and investigate this unique form of genome regulation, researchers will use innovative in vivo and in vitro platforms. Project findings could help resolve long-standing paradoxes in epigenetics research and provide a complete model of epigenetic transformation with direct disease implications.
Objective
DNA methylation is a tightly controlled mechanism that is essential for normal development and genome regulation. Although maintained in a highly static pattern across healthy tissues, DNA methylation is globally reprogrammed in nearly all malignant cancers, including gains at thousands of gene promoters and global loss across large domains. Substantial work from our group to characterize multiple primary tumor cohorts, transgenic animal models, and cancer cell lines finds that current experimental systems rarely, if ever, capture key features of the cancer epigenome. In contrast, our parallel efforts to understand epigenetic dynamics in development suggest an alternative, highly innovative hypothesis with a clear path for investigation. We find that the epigenetic alterations in cancer very closely mirror patterns that emerge in the early placenta, a tissue that naturally acquires invasive, immune suppressive, angiogenic, metabolically plastic and mutationally tolerant properties. Notably, this cancer-like epigenome depends on dynamic, previously undiscovered configurations of regulators that can be triggered without genetic mutation. With these insights, we have innovated tractable in vitro and in vivo platforms to dissect the biochemical, genetic, and physiological properties of this unique form of genome regulation as it supports developmental processes. We believe these efforts will demonstrate that the placenta and by extrapolation the cancer epigenome reflect a switch-like reprogramming event that can be studied at high resolution. In line with the ERC-ADG program’s goals, we will pursue ambitious and critical questions, resolve long-standing paradoxes and provide a complete model of epigenetic transformation in development with direct disease implications. Our world-class interdisciplinary team, extensive preliminary data, experimental design and proven track-record will enable us to turn this grant into high-impact and translationally relevant discoveries.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine obstetrics
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics epigenetics epigenomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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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.
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.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2022-ADG
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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.
80539 MUNCHEN
Germany
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.