Objective
TET2 (Tet Methylcytosine Dioxygenase 2) is a DNA demethylase frequently mutated in patients with Acute Myeloid Leukemia (AML). DNA methylation is an epigenetic modification with key roles in the specification of cellular identity, and, when deregulated, in cancer. DNA methylation is a reversible process and, only recently, it was discovered that TET (Ten-eleven Translocation) proteins mediate DNA demethylation. Mammals have three TET homologues (TET1-3). While TET1 and TET3 share an N-terminal DNA-binding domain (CXXC motif), TET2 has lost its CXXC motif during evolution. Therefore, it is not understood how TET2 binds DNA. Due to the lack of a known DNA-binding domain in TET2, I hypothesize that TET2 may require to interact with proteins to be recruited to DNA, which is essential for its function.
Hence, the main goal of my proposal is to understand how TET2 binds to DNA and to identify interacting proteins that participate in this recruitment. I also aim to unveil whether cancer-associated mutations affect TET2 recruitment.
To achieve these goals, I will perform a structural-functional analysis of TET2. First, I will perform Chromatin Immunoprecipitation (ChIP) followed by whole genome sequencing of wildtype and truncated TET2. Thus, I will identify the region(s) required for the binding of TET2 to DNA. Next, I will seek proteins that interact with TET2 through the previously identified region by Mass Spectrometry and I will test their involvement in TET2 recruitment to DNA. Furthermore, I will perform similar experiments to inspect the impact of TET2 missense mutations found in human cancer on TET2 recruitment to DNA.
Altogether, this project will yield a better understanding of how TET2 is recruited to DNA. The results obtained will significantly impact the epigenetic field and allow for a better understanding of the mechanisms by which TET2 exerts its function in normal cells and how TET2 mutations contribute to 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: 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 DNA
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine oncology leukemia
- natural sciences chemical sciences analytical chemistry mass spectrometry
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
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-EF-ST - Standard EF
See all projects funded under this funding scheme
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-2017
See all projects funded under this callCoordinator
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.
1165 KOBENHAVN
Denmark
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.