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Projekt Druckansicht

Identifizierung und Charakterisierung Ovar-exprimierter Rezeptormoleküle und Transposon-basierte Keimbahntransformation in Schistosoma mansoni

Fachliche Zuordnung Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
Förderung Förderung von 2008 bis 2016
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 70510307
 
Erstellungsjahr 2016

Zusammenfassung der Projektergebnisse

With respect to the scientific questions and aims of the project we reached most of the targets. A number of cytoplasmic and membrane-bound molecues was identified and characterized that contribute to gonad differentiation processes in adult S. mansoni. In this context molecular and biochemical evidence were obtained for a complex interaction between Smβ-Int1 and SmVKR1. Besides the identification of downstream binding partners and ligands activating SmVKRs, we demonstrated the ligand-independent activation of SmVKR1 by Smβ-Int1 which is supported by the bridging molecules SmILK, SmPINCH, and SmNck2. Furthermore, we unraveled the functional meaning of Smβ-Int1/SmVKR1 cooperation, which is involved in differentiation processes during oogenesis also by controlling directed apoptosis in oogonia and further processes leading to cell death in primary oocytes. Alongside we recognized why schistosome genes are often problematic to be expressed in heterologous systems. Based on our findings a solution was developed to overcome these problems, which will be of high value in the future – not only for schistosome research. Although a protocol for germline transformation was successfully developed, generating stably transformed schistosomes by a transposon-based approach is still in progress. With respect to applied aspects of this basic research approaches, our results characterizing molecules that control the reproductive biology of schistosomes elucidated the prominent role of kinases. They represent Acilles´ heels for schistosomes - not only with respect to reproduction. This fact vouches for exploitable biology against the background of the roles of kinases for diverse human diseases, their druggability, the high number of kinase inhibitors being available, and the increasing molecular and structural knowledge about kinases in schistosomes.

Projektbezogene Publikationen (Auswahl)

 
 

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