Objective
The regulation of gene transcription governs eukaryotic cell growth and differentiation. Despite its importance, transcription regulation is not understood at a mechanistic level. Regulation occurs mainly during initiation, when the enzyme RNA polymerase II (Pol II) assembles with ~50 polypeptides on promoter DNA. Regulatory signals are transmitted by the 25-subunit Mediator, and convert the initiation complex into a productive elongation complex. Ten years after the solution of the Pol II structure (Cramer et al., Science 2000, 2001), elongation is understood, but the structure and regulatory control of the initiation complex remain largely unknown. Here I propose to solve this central problem of molecular genetics and obtain a movie that shows how a gene is activated. Our recent structure of Pol II with initiation factor TFIIB (Kostrewa et al. Nature 2009) provides the starting point for the proposed risky and challenging structure-function analysis of regulated initiation. First, we will determine structures of Pol II in the initiating state. Second, we will solve the structure of the essential, gene-regulatory 7-subunit head module of the Mediator core. Third, we will establish ¿nascent transcriptome analysis¿ as a novel technique that measures mRNA synthesis rates globally, and will use it to probe the mechanisms of regulated initiation by structure-based mutagenesis in vivo. Expected results will open new horizons for investigating the function of eukaryotic genomes, and will have a strong impact on biomedicine, since deregulated transcription underlies many diseases, including cancers and certain metabolic dysfunctions. This ground-breaking research requires the long-term, flexible commitment of the ERC, to successfully compete with teams in the US and Japan.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences molecular biology molecular genetics
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences genetics genomes eukaryotic genomes
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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-2010-AdG_20100317
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
80539 MUNCHEN
Germany
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.