Objective
Intra-tumoral heterogeneity allows all form of cancers to undergo an evolutionary process in response to selective pressures, such as therapy, which results in a more aggressive disease. As chronic lymphocytic leukemia (CLL) are particularly amenable to evolutionary investigations, it has been shown that CLL’s capacity to escape therapy is linked in to genetic evolution, which is fueled by intra-tumoral heterogeneity. Aberrant DNA methylation can also dysregulates genes involved in CLL pathogenesis. Like genetic alterations, DNA methylation modifications are heritable and subject to natural selection. Landau et al have studied sub-population DNA methylation heterogeneity in CLL and uncovered a large amount of stochastic variation. The acquisition of stochastic DNA methylation alterations enhances epigenetic plasticity and creates a non–genetically encoded source of heterogeneity, fuelling tumour cells in their search for superior evolutionary trajectories. These new data modify the way we understand cancer epigenetics, and offer a new field of investigation: identify “epidrivers”, i.e. somatic epigenetic alterations leading to cancer-heterogeneity and which are positively selected through cancer evolution.
Thus, I will pursue in this project four independent yet complementary aims. During my outgoing period I will robustly identify epidrivers from bulk next-generation sequencing (NGS) (Aim 1) and from single-cell NGS (Aim 2) of a large CLL cohort. Candidate epidrivers uncovered from the first two aims, will be further validated in a large-scale epigenome editing screen (Aim 3). Then building upon technological development from Aim 2 and 3, during my returning period at Curie Institute, I will extend this important paradigm to solid tumor by exploring breast cancer evolution (Aim 4).
This integrative analysis of epigenetic heterogeneity will enable the reconstruction of tumor epigenetic population complexity and how it shapes disease relapse and evolution.
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 evolutionary biology
- medical and health sciences clinical medicine oncology breast cancer
- natural sciences biological sciences genetics epigenetics epigenomes
- medical and health sciences clinical medicine oncology leukemia
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.
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.
-
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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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-2016
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.
75231 Paris
France
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.