Project description
A closer look at cancer triggers
Cancer often involves genomic instability, caused by errors during cell division. Despite its importance, we know little about non-genetic factors driving tumours. In this context, the ERC-funded MitErrA project aims to explore these gaps by studying how mitotic errors, like micronuclei, affect cells. Specifically, it will answer questions about chromatin state changes, transcriptional regulation, genome organisation, and the physiological impact of abnormal chromosomes. By leveraging cutting-edge techniques like live-cell imaging and single-cell genomics, MitErrA will investigate how these errors drive cellular adaptation and potentially fuel cancer. This research promises to offer groundbreaking insights into non-genetic drivers of tumorigenesis.
Objective
One of the holy grails in cancer biology is to understand how genomic instability, a hallmark source of mutagenesis, arises. However, surprisingly little is known about non-genetic drivers of tumorigenesis. My proposal will delve into the old question of how Mitotic Errors and nuclear Abnormalities (MitErrA) affect cellular homeostasis, from a fresh perspective: the elucidation of non-genetic effects on genome function and cellular adaptation.
I recently discovered that micronuclei, a prominent type of errors in mitosis, are a previously unappreciated source of epigenetic instability. This discovery, together with the novel technologies that I developed, will serve as the springboard to address four fundamental questions:
1) How is chromatin state affected in abnormally segregated chromosomes?
2) What are the mechanisms of transcriptional (dys)regulation following errors in mitosis?
3) How is genome organization perturbed in imbalanced genomes?
4) What is the physiological significance of abnormal chromosomes generated by mitotic errors?
I will combine cutting edge techniques, such as targeted chromosome manipulation and single-cell genomics, with advanced systems to track mis-segregated chromosomes by live-cell imaging over multiple generations. I will identify additional sources of inherited abnormal nuclear structures (termed Mit-bodies) and characterize their DNA damage/repair dynamics and epigenetic alterations. I will study how transcription dynamics are perturbed in daughter cells upon abnormal mitosis and define higher-order genome organization, nuclear positioning and lamina association of mis-segregated chromosomes. Finally, I will investigate long-term cellular adaptations and assess the tumorigenic potential of these abnormal chromosomes. Altogether, these studies will offer the first comprehensive assessment of the non-genetic mechanisms by which errors in mitosis may drive cellular adaptation and tumorigenesis.
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
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine physiology homeostasis
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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
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-STG
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55128 Mainz
Germany
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