Objective
Epigenetic reprogramming is a hallmark of brain cancer. Remarkably, driver mutations of the histone H3.3 variant and its loading machinery have been recently found in paediatric glioblastoma multiforme (GBM), a devastating neoplasm originating from transformed neural precursors. Thus, the very basic building blocks of chromatin can be mutated in cancer.
The present challenge is to define at which level altered H3.3 loading influences GBM pathogenesis and provide clues into the underlying mechanisms. Based on work from our group and others, we hypothesise that alterations of H3.3 function/deposition would lead to epigenetic changes, deregulated transcription at bivalent loci and other genomic regions, and alterations of telomere maintenance mechanisms, in turn contributing to tumourigenesis.
The main objectives of this proposal are to:
1. Examine the impact of H3.3 mutations on brain cancer pathogenesis, by determining the effect of mutant H3.3 expression on neural precursor cell transformation (A), and tumour maintenance (B).
2. Define the molecular changes caused by incorporation of H3.3 mutants into the genome and their involvement in tumourigenesis, by A. determining the genome-wide distribution of WT and mutant H3.3 proteins, B. identifying mutant H3.3-driven transcriptional and epigenetic changes, C. defining effects on telomere maintenance mechanisms, and D. connecting mutant H3.3-driven molecular changes to the biological phenotypes.
The discovery of mutations in histones and their loading machinery represents a paradigm change in the field of cancer epigenetics. We anticipate this study to provide key insights into the role of these alterations in chromatin regulation and cancer pathogenesis. More broadly, this work will increase our understanding of the fundamental mechanisms governing chromatin modification in mammalian cells.
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 biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences genetics epigenetics
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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.
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.
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.
ERC-2013-CoG
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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.
Host institution
53127 Bonn
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.