Project description
Epigenetic drivers in metastasis
Cancer development involves complex biological processes, driven by genetic mutations and epigenetic changes. Epigenetic changes are modifications that regulate gene expression without altering the DNA sequence, involving mechanisms like DNA methylation, histone modification, non-coding RNAs, and chromatin remodelling. Epigenetic changes are emerging as key players in the metastatic transition of cancer cells. Funded by the Marie Skłodowska-Curie Actions programme, the EpiMetaPDO project will employ patient-derived organoids generated from primary and metastatic colon cancer to study changes at the chromatin level. Researchers will determine histone modification and identify key transcription factors involved in the process, providing fundamental knowledge into the mechanisms of cancer evolution.
Objective
Cancer development is a convoluted biological process that reshapes cellular identity. Genetic mutations are crucial in driving such process, yet fail to fully explain metastatic transition—a critical step in cancer evolution. For this reason, reprogramming driven by non-mutational epigenetic changes is increasingly recognized as a potential mechanism by which cancer cells acquire metastatic properties. Despite the genetic heterogeneity, specific transcriptional programs are activated to promote the acquisition of such properties. Therefore, understanding the role of changes at the chromatin level in facilitating metastatic transitions becomes crucial.
To address this, I will use patient-derived organoids (PDOs) generated from primary colon cancer and various metastatic sites. PDOs are an optimal model system available in the hosting laboratory, providing a platform for investigation and subsequent functional validation. The project’s first goal is to profile changes in histone modifications and in the enhancer interactome, in primary and metastasis PDOs. This will identify chromatin states transitions and cis-regulatory elements with a key relevance in metastatic progression and maintenance (Aim 1). Transcription factors (TFs) with potential regulatory roles in these processes will be identified by integrating chromatin accessibility data and performing footprinting analysis (Aim 2). Functional validation of candidate TFs will be conducted using CRISPR perturbations, combined with single-cell multi-omic readout and in-vitro assays to assess PDOs' fitness and invasiveness potential (Aim 3). Altogether, in this project we will employ a comprehensive approach to investigate the molecular mechanisms underlying the activation of pro-metastatic gene regulatory networks, providing insights into the epigenetic drivers of metastatic transitions.
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 mutation
- medical and health sciences clinical medicine oncology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2023-PF-01
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20139 Milano
Italy
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