Objective
In B cells, antibody repertoire is created via two DNA instability complexes, one of which uses DNA cytosine deamination and is needed for immunoglobulin (Ig) diversification. Targeting of DNA deamination is poorly understood and mis-targeting can lead to genetic pathologies. Activation induced deaminase (AID) catalyses the hydrolytic deamination of cytosine residues, with the resulting uracil inducing DNA instability leading to Ig diversification. Recently AID has been implicated in inducing developmental DNA demethylation and pluripotent stem cell formation. Although transcription had been implicated in these mechanism, no direct evidence existed linking AID activity and transcription.
The aim of this application is the analysis of AID containing transcription complexes and the role of RNA pol II modification during Ig diversification and epigenetics. Proteomic analysis of AID containing complexes from cytoplasm, nucleoplasm and chromatin revealed distinct associations, with the chromatin complex containing subunits of the elongating RNA pol II, transcription elongation and chromatin remodelling complexes. Biochemical analysis in vitro and in cell lines will identify direct interactions and domains and subsequent in vivo reconstitution of AID mutants determining in vivo relevance. Genetic analysis of candidates using transgene and knockout in cells and mice will delineate the molecular pathways of how transcription can alter the targeting or efficiency of AID. To further determine the role of the candidates on the loci, various forms of ChIP analysis will be utilised (e.g. double ChIP & ChIP-Seq); including the effect of RNA pol II modification, chromatin markers, and associated factors.
Conclusions of this study will provide novel and detailed insight into the molecular mechanisms of AID regulation and how this will effect immune diversification and epigenetics, while providing new drug targets for AID pathologies (i.e. cancer and autoimmunity).
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 medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
- natural sciences biological sciences genetics RNA
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-2010-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
20139 Milano
Italy
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.