Genetics of mechanosensation

Coordinator:		Prof. Dr. med. Ralph Knöll
Institution:		Herzzentrum Göttingen
Homepage:		www.herzzentrum-goettingen.de

Mechanosensation is the process whereby the cell initially transforms changes in its shape and structure and initiates first steps to convert these changes into biochemical signals. Previously we have been able to identify the muscle LIM protein (MLP) together with t-cap and titin as a macromolecular complex involved in mechanosensation in cardiomyocytes. However, not all aspects of cardio-mechanosensation can be explained by this signalosome and additional proteins have to be present in this complex. For example, Z-disc – transcriptional coupling and their relationship to diastolic dysfunction remain completely unexplained.
Therefore the following aspects will be studied in this project:
•    Relevance of human mutations in genes involved in cardiac mechanosensation
•    New therapeutic approaches to treat this disesase (kinase inhibitors, calcineurin or phosphatase inhibitors)
•    Structural analysis of new components involved in mechanosensation (new yeast two hybrid screens)
•    Zebrafish analysis (fast approach regarding in vivo function)
•    Generation and analysis of novel genetically altered mouse models
•    Epigenetics of mechanosensation
•    Mechanosensation and diastolic dysfunction
•    Interactom, Proteom and Proteomics of mechanosensation