Project description
Real-time study of chromosomal instability in cancer
Many genomic aberrations originate from mistakes during cell division, in which the DNA is normally divided equally to both daughter cells. There is a lack of understanding regarding the genetic consequences of mitotic errors for tumourigenesis and genomic instability. Patient-derived tumour organoids and cutting-edge research technologies combining direct microscopic observation of mitosis and single-cell whole-genome sequencing provide an opportunity to study these fundamental questions. The EU-funded OCIC project will study the occurrence and maintenance of genomic instability using organoids derived from esophageal adenocarcinoma (EAC) patients as a model system. The EAC genomes, in particular, show genomic catastrophes that might drive tumourigenesis. Ultimately, the study aims to apply the technology to a panel of human tumour organoids derived from different tissues.
Objective
Genomes from tumor cells are often grossly derailed in DNA content, with chromosomes gained, lost, fused or otherwise rearranged. Presumably, many of these aberrations stem from mistakes during cell division, during which the DNA is normally divided equally to both daughter cells. Cell division is often studied microscopically in 2D cell culture, while DNA sequences from cancer genomes are often re-constructed from tumor patient material. As a consequence, there is still a poor understanding regarding the direct genetic consequences of mitotic errors and as such, genomic instability. Patient-derived tumor organoids, in combination with cutting-edge technology that combines direct microscopic observation of mitotic events, with single-cell whole genome sequencing (scWGS), provide a unique opportunity to tackle these fundamental questions.
To understand the occurrence and maintenance of genomic instability, I will study organoids derived from esophageal adenocarcinoma (EAC) patients. While observed in many cancers, EAC genomes in particular show genomic catastrophes and are thought to drive tumorigenic transformation. Cells will be filmed in real-time to detect mitotic errors. Daughter cells from erroneous divisions will be photoconverted, allowing single cell tracking and isolation for prospective genetic analysis. scWGS will detect imbalances in chromosome number and/or structural rearrangements between the paired daughter cells. Genetic aberrations can be directly linked to the observed mitotic error and cell fate across multiple divisions to understand its role in tumorigenesis.
To couple molecular mechanisms to genetic footprints, fluorescent markers will be implemented to interrogate the type of DNA damage missegregated chromosomes receive, how this affects the subsequent cell cycles, and how this missegregated DNA is re-incorporated into the genome. Finally, I will test these findings across a panel of human tumor organoids derived from different tissues.
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.
- medical and health sciences clinical medicine oncology prostate cancer
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
3584 CX Utrecht
Netherlands
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.