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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-IIF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
10117 Berlin
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.