Objective
Acquired immunity to foreign pathogens depends on functional B and T cells. The objective of this proposal is to elucidate the transcriptional control of lymphocyte development at three stages by deciphering the transcriptional networks specifying pro-B and pro-T cells in early lymphopoiesis and plasma cells in terminal B cell differentiation.
To this end, we generated knock-in mice carrying a biotin acceptor sequence at the C-terminus of transcription factors, which can be biotinylated by transgenic co-expression of the E. coli biotin ligase BirA. In vivo biotinylation facilitates antibody-independent precipitation of these transcription factors by streptavidin pulldown (Bio-ChIP). Preliminary Bio-ChIP sequencing experiments validated this approach for genome-wide identification of transcription factor target genes.
Bio-ChIP sequencing will be used to identify the target genes of key transcription factors controlling the development of pro-B cells (Ikaros, E2A, STAT5, EBF1, Pax5, PU.1 IRF4), pro-T cells (Notch1, RBP-J, GATA3, Ikaros, E2A, STAT5) and plasma cells (Blimp1, IRF4, XBP1). RNA sequencing of wild-type and mutant lymphocytes will determine the regulated target genes of these factors, which are ultimately relevant for the elucidation of transcriptional networks. The function of selected target genes at central nodes of these networks will be analyzed by the latest miR30-shRNA knockdown technology. Finally, regulatory complexes interacting with these transcription factors will be identified by streptavidin-pulldown purification and mass spectrometry followed by their integration into the transcriptional networks by ChIP-seq mapping to the transcription factor target genes.
These experiments will provide fundamentally new molecular insight into the generation of all three lymphocyte stages and will contribute to a better understanding of how deregulation of the transcriptional control promotes the development of lymphoid malignancies.
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 RNA
- 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.
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.
ERC-2011-ADG_20110310
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.
Host institution
1030 Wien
Austria
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.