Obiettivo Kidney dysfunction is central to hypertension. Mutations in the WNK/SPAK-OSR1 pathway cause human hypertension by modulating salt transport. Yet, just when the physiological actions of these proteins appear clear, contradictory data raise questions about their effects, and leave investigators confused about physiological roles and mechanisms of disease. Here, we propose to develop a novel zebrafish model system to permit us to study how NaCl transport is regulated.Our groups have used variety of approaches to study the thiazide-sensitive Na-Cl cotransporter (NCC) over time. We have, however, been frustrated by the inability to study mechanisms of transporter regulation in situ. Organismal solutions to problems of terrestrial life, however, often evolved from challenges encountered during aquatic life. Fish electrolyte homeostasis is maintained, therefore, by a panoply of proteins that are conserved. Fish kidney develops first as pronephros with tubules homologous to nearly every mammalian nephron segment. Studying the pronephros offers excellent experimental conditions throughout.Here, we propose to utilize the unique morphological resources available through the Bachmann group to develop a zebrafish model to study salt transport regulation. We plan to use the simple organization of the pronephros to establish a three dimensional model of the signaling proteins involved in regulating NCC activity. Work will be organized in collaboration with zebrafish specialists at the Max Delbrück Centrum (MDC) in Berlin. Specifically, we will,1. Analyze zebrafish NCC and NCC-like 2 expression, localization, phosphorylation, and activity2. Determine effects of NCC and NCC-like 2 knockdown3. Determine effects of WNK4 and OSR1 knockdown on NCC and NCC-like 24. Determine how distinct ion loads affects the NCC signaling complex.The transfer of knowledge in hypertension research to the European host and to European collaboration partners, will be central to this project. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2012-IIF - Marie Curie Action: "International Incoming Fellowships" Invito a presentare proposte FP7-PEOPLE-2012-IIF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IIF - International Incoming Fellowships (IIF) Coordinatore CHARITE - UNIVERSITAETSMEDIZIN BERLIN Contributo UE € 111 889,20 Indirizzo Chariteplatz 1 10117 Berlin Germania Mostra sulla mappa Regione Berlin Berlin Berlin Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Anja Stielow (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
