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Content archived on 2024-05-29

Structural and functional determinants of GRK2 in cardiac development

Objective

G protein-coupled receptor kinases (GRK) provide the rate-limiting step for terminating incoming signals at G protein-coupled receptors (GPCR) to protect the cell from over-stimulation. GRK2, the most commonly expressed GRK, has been shown to regulate hear t function in the adult and during development as GRK2 knockout (KO) mice die during embryonic development. Since the reason for the embryonic lethality has been analysed only preliminary, I want to uncover the molecular mechanism to provide a biochemical explanation for the action of GRK2 in ensuring normal cardiac development and in the course of cardiovascular diseases.

The aims of the project are:
1) Generation of a GRK2 knockdown in zebra fish and its histological and biochemical characterization.
2) De termination of the GRK2 structures relevant for the assessed phenotype.
3) Investigation of affected signalling cascades.
4) Transfer of the zebrafish results back to mice.

The novelty of the project is based on a combined in vivo approach to explain the bio chemical function of a protein of highest relevance in man by using a second model organism instead of extrapolating in vivo relevance from in vitro or cell culture studies. To accomplish this, I will be trained in manipulating and analysing zebra fish and in techniques commonly used in signal transduction such as site-directed cloning and biochemical assays, which will complement my previous research experience in mice and chicken embryos. In addition, I will not only widen my international experience in research, but also my personal horizon.

Therefore, the Marie Curie Out-going International Fellowship will serve my professional growth by enabling me to gain knowledge in the investigation of signal transduction and the handling of a third model organism, giving me the possibility to choose the technique and the organism whichever is best for the question I want to address in my future independent research career in Europe.

Fields of science (EuroSciVoc)

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Keywords

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Topic(s)

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Call for proposal

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FP6-2004-MOBILITY-6
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Funding Scheme

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OIF - Marie Curie actions-Outgoing International Fellowships

Coordinator

UNIVERSITAETSKLINIKUM FUER DIE MEDIZINISCHE FAKULTAET DER ALBERT-LUDWIGS-UNIVERSITAET FREIBURG
EU contribution
No data
Total cost

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No data

Participants (1)

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