Project description
Chromosomal translocations and nuclear function
Cancer is often associated with chromosomal translocations, a phenomenon whereby a chromosome breaks, and its fragments reattach to another chromosome. This may interrupt tumour-suppressor genes or more often create fusion genes or proto-oncogenes at the translocation breakpoint, leading to oncogenesis. The working hypothesis of the EU-funded LymphoTOP project is that chromosomal translocations disturb genome architecture and may cause further deregulation. Researchers will focus on non-Hodgkin lymphoma and determine how translocations in immunoglobulin genes may affect the genomic and epigenetic landscape and lead to the disease. Results will provide fundamental knowledge on nuclear function and carcinogenesis.
Objective
A central goal in cancer research is to identify the molecular mechanisms underlying tumor formation, such as translocations that result in expression of fusion genes or proto-oncogenes located at the translocation breakpoints. While the consequences of this erroneous expression have been widely studied, other effects of translocations remain largely unexplored. Nevertheless, these can provide vital new insights into tumorigenesis. I hypothesize that translocations disturb the global 3D genome architecture, causing alterations in chromosome territory positioning and interchromosomal interactions. And, that these can account for (in)activation of key genomic loci for which the cause of deregulation remains so far unknown. I will address this hypothesis in the context of Non-Hodgkin lymphoma (NHL)-related immunoglobulin (IGH) translocations. By genome editing we will create lymphoblastoid cell lines and cord blood cell-derived B lymphocytes in which IGH translocation-based effects can be cleanly dissected in vitro and in vivo. In these models, we will study how IGH translocations affect genome topology, the epigenetic and gene expression landscape and NHL formation. To that end, we will assess (i) chromosome territory structure and interchromosomal crosstalk by chromatin conformation capture and fixed- and live-cell imaging, (ii) epigenetic and gene expression maps using bulk and single-cell profiling and (iii) in vivo tumor formation. Importantly, after exploring the presence of the observed gene expression changes in NHL samples, we will target the coinciding changes in in vitro and in vivo approaches to probe their relevance for lymphomagenesis. Overall, LymphoTOP shall lead to deeper insights into translocation-based genome topology reorganisation and its role in tumorigenesis, and to potential identification of new vulnerabilities of lymphomas. Thus, extending its impact to many fields, from lymphoma and tumor biology to 3D genome organisation and beyond.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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.
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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-2021-STG
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08003 Barcelona
Spain
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