In vivo Bedeutung des MAPK-Signalweg-Inhibitors SPRED - Charakterisierung der Funktion durch "knockout"-Modelle

• Applicant: Professor Dr. Kai Schuh
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2007 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 50193000

Aim of this project is to elucidate the versatile and complex functions of SPRED proteins in vitro but also in an intact organism. Based on our previous work, we intend:1. To clarify the mechanism responsible for the elevated stress hormone production in SPRED2 KO mice, which is associated with OCD-like behaviour. We intend to investigate the behaviour, electrophysiological properties of synapses in the amygdala, and anatomical characteristics of KO mice.2. To circumvent the obvious functional compensation of SPRED proteins by other family members and the embryonic lethality of double knockouts through generation of inducible or tissue-specific kncokou models for SPRED1 and -2.3. To verify the protein/protein interaction of SPRED2 with Tubulins, which was identified by pull-down assays and subsequent mass spectrometrical analyses. On the molecular level, we would like to investigate if SPRED2 might regulate Tubulin polymerisation or if SPRED2 might by functionally involved in the regulation of vesicle transport along microtubules. This interaction may be part of a fundamental process in biology and may, therefore, be of high relevance for our understanding of intracellular transport in eukaryotic cells.The animal models offer the possibilty to reassess the molecular observations in a physiological context in entire organism.

• DFG Programme: Research Grants