Objective
DNA methylation is integral to the regulation of gene transcription but is deregulated in cancer. Mechanisms causing this dysregulation are however poorly understood. Although DNA methylation mechanisms were described for several decades ago, the enzymes responsible for DNA demethylation were only discovered a few years ago: TET enzymes catalyze the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) through a reaction requiring oxygen and 2-oxoglutarate (2OG). Interestingly, decreased oxygen concentrations (hypoxia) are common in cancer, as is an altered 2OG metabolism.
Hypoxia induces the activity of Hypoxia Inducible Factor (HIF) transcription factors, which alter gene expression in cells to counter and cope with hypoxia. It is however poorly characterized how DNA methylation influences HIF binding, and how HIF in turn interfaces with the epigenome.
In CHAMELEO, we aim to investigate the influence of hypoxia on the epigenome and the resulting phenotypic response in cancer. Firstly, we hypothesize that promoters of tumor suppressor gene can be hypermethylated through inhibition of DNA demethylation at low oxygen concentrations, thus contributing to oncogenic transformation. To investigate this, we will study the dependence of TET DNA hydroxylases on oxygen and 2OG, as well as the overall and locus-specific changes upon hypoxia of their product (5hmC). Secondly, because much of the hypoxic response is executed through HIFs, we will investigate how HIF binding is influenced by DNA methylation and how HIFs interface with epigenetic modulators such as TETs. Experiments in vitro and in vivo will be combined with state-of-the-art high-throughput sequencing techniques, and are expected to provide an unambiguous and comprehensive view on the role of DNA methylation dynamics in hypoxia and cancer.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- natural sciences chemical sciences electrochemistry electrolysis
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.
FP7-PEOPLE-2012-CIG
See other projects for this call
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
9052 ZWIJNAARDE - GENT
Belgium
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.