Objective
Tumorigenesis is an evolutionary process driven by gradual mutation acquisition to confer selective advantages to somatic cells. DNA rearrangements are the most common cancer driver mutation, outnumbering base substitutions. Rearrangements amplify, disrupt and fuse genes or alter their gene regulation, ultimately driving adaptive changes to initiate cancer, metastasis and therapy resistance. Cancer genomics has revealed that most of these alterations arise as complex genomic rearrangements (CGRs), where a multitude of changes arise in a short time. While in most cases deleterious to the cell, in rare cases CGRs confer an adaptive malignant phenotype in one giant-leap through saltatory evolution events (SEEs) reminiscent of the hopeful monsters theorised by Goldschmidt. Given their potential to overcome strong selective barriers, it has been proposed that SEEs draw the line between benign lesions and lethal cancer, and understanding their mechanisms is thus fundamental to tumour biology. However, the identity of cells undergoing SEEs has remained elusive, with cancer genomics studies focusing typically on long-established cancers rather than early or even initiating cancer cells. Intriguingly, CGRs are largely explained by cascades of atypical cell nuclei (i.e. nuclear atypias) fueling rearrangement formation, providing an opportunity to study SEEs.
Building a novel automated AI-driven framework that couples imaging and single-cell multi-omics, we will leverage nuclear atypias as a phenotypic indicator to dissect principles and mechanisms of SEEs in the making, and advance fundamental cancer biology. Using highly controllable cell lines and organoid models of colorectal cancer (CrC), a tumour thought to be driven by SEEs, we will unravel pathways, genetic contexts and chromosome-level constraints determining SEEs. Finally, via validation in patient samples we will pave the way to determining SEEs in future clinical studies to advance precision oncology.
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.
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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)
MAIN PROGRAMME
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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.
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.
69117 Heidelberg
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.