NOVEL KIDNEY MODEL

zebrafish model to study human hypertension

Coordinatore	CHARITE - UNIVERSITAETSMEDIZIN BERLIN    more  Organization address address: Chariteplatz 1 city: BERLIN postcode: 10117 contact info Titolo: Ms. Nome: Anja Cognome: Stielow Email: send email Telefono: +49 30 450576059 Fax: +49 30 450576954
Nazionalità Coordinatore	Germany [DE]
Totale costo	111˙889 €
EC contributo	111˙889 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-IIF
Funding Scheme	MC-IIF
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-10-23   -   2014-10-22

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CHARITE - UNIVERSITAETSMEDIZIN BERLIN  Organization address address: Chariteplatz 1 city: BERLIN postcode: 10117 contact info Titolo: Ms. Nome: Anja Cognome: Stielow Email: send email Telefono: +49 30 450576059 Fax: +49 30 450576954	DE (BERLIN)	coordinator	111˙889.20

Mappa

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 Obiettivo del progetto (Objective)

'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 activity 2. Determine effects of NCC and NCC-like 2 knockdown 3. Determine effects of WNK4 and OSR1 knockdown on NCC and NCC-like 2 4. 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.'

Introduzione (Teaser)

Kidney dysfunction leads to hypertension, which in turn creates more damage to the kidneys. An EU study addressed the mechanisms of salt transport regulation in kidneys using a model system.