Objective
Serum response factor (SRF) regulates the expression of immediate-early genes as well as the expression of many muscle-specific genes. Differential regulation of the expression is achieved by exclusive binding of specific coactivators. MAL and MKL2, two coactivators of the myocardin family link SRF activity to a Rho-actin signalling pathway. Their activity is controlled through regulated interaction with G-actin, which is mediated by an RPEL domain. Rho-activation and G-actin depletion leads to accumulation of MAL in the nucleus where it activates transcription. Recent results show, that actin binding controls MAL activity at multiple levels. Actin binding inhibits MAL nuclear import, promotes MAL nuclear export and inhibits transcriptional activation by MAL. A major unresolved question is the mechanism by which actin binding regulates these events. In the proposed project, I will address this question by developing a system to track MAL in real time and study the interactions between MAL and actin and between MAL and SRF in live cells. I plan to use FRET/FLIM to assess the real time dynamics and changes in the localisation of MAL-actin interactions and the interaction of isolated RPEL domain with actin. I will investigate the stoichiometry of MAL-actin interaction, in vivo as well as in vitro. I will use FRAP analysis to assess changes in the mobility of MAL following stimulation, and compare the kinetics with that previous obtained for the MAL-actin interaction by FRET, and perform detailed in vitro actin binding studies. Additionally, I plan to elucidate actin’s interaction with members of the other family of RPEL motif-containing proteins, the Phactr/Scapinin family. By applying this wide variety of biophysical techniques I hope to understand the mechanism of the actin-dependent regulation of MAL activity in more detail.
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 biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
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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.
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-2007-2-1-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
E20 1JQ LONDON
United Kingdom
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.