Objective
B-cell differentiation is a complex process in which epigenetic changes, i.e. DNA methylation and histone modifications, play an essential role to regulate gene expression. Disturbances in epigenetic processes can result in development of B-cell malignancies, such as mantle cell lymphoma (MCL). So far, little is known about the epigenetic alterations underlying MCL. In general, epigenetic studies in cancer have mainly dealt with identification of hypermethylated promoter regions. Recent genome-wide studies in B cell malignancies however, have shown that the majority of DNA methylation changes do not occur in promoter regions but at intra- and intergenic loci, which are enriched for enhancers. In this project, I wish to study the functional impact of DNA methylation changes at these enhancer regions on DNA looping and gene expression regulation in MCL. To achieve this goal, I will generate genome-wide chromosome conformation maps of MCL and normal naive B cells using Hi-C sequencing. Additionally, I will generate DNA methylation profiles, histone modification maps and gene expression profiles of these samples. Combining these datasets will allow identification of intra- and intergenic enhancer regions that, based on differences in DNA methylation status, affect DNA looping and gene expression. The effect of DNA methylation on enhancer activity of these regions will then be studied in further detail using luciferase reporter assays. The proposed study shall give insights into (i) the effect of DNA methylation outside promoter regions on DNA looping and gene expression (fundamental aspect); (ii) the DNA methylation changes in MCL that affect these processes (biological aspect); and (iii) the functional impact of differential DNA methylation between MCL subtypes (clinical aspect). The latter 2 shall lead to better understanding of the underlying molecular mechanisms of MCL and may form a basis to design new therapeutic strategies for this aggressive disease.
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
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
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.
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-IEF
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.
Coordinator
08036 Barcelona
Spain
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.