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SYSCILIA

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A systems biology approach to dissect cilia function and its disruption in human...

A systems biology approach to dissect cilia function and its disruption in human genetic disease AIM: To identify the molecular mechanisms characterizing cilium function, and the discrete perturbations associated with dysfunction caused by mutations in inherited ciliopathies, applying a systems biology approach. BACKGROUND: C... ver más

31/05/2015

STICHTING RADBOUD...

15M€

Presupuesto del proyecto: 15M€

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STICHTING RADBOUD UNIVERSITEIT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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19 Participantes

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UEVE

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Líder del proyecto

STICHTING RADBOUD UNIVERSITEIT No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 15M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto AIM: To identify the molecular mechanisms characterizing cilium function, and the discrete perturbations associated with dysfunction caused by mutations in inherited ciliopathies, applying a systems biology approach. BACKGROUND: Cilia are microtubule-based, centriole-derived projections from the cell surface. They transduce extracellular signals and regulate key processes in which signals of the extracellular environment are translated into a cellular response, such as cell cycle control, Wnt signalling, Shh signalling and planar cell polarity. Disruption of cilium-based processes by mutations can cause very severe disorders. Many of these ciliopathies have overlapping phenotypes. There is evidence, that ciliary proteins are organized in cell/context specific complexes and/or in shared regulatory circuits in cilia of affected tissues. Yet, knowledge of the composition, wiring, dynamics and associated signaling pathways of the corresponding molecular building blocks and associated protein networks remains very limited. APPROACH: We propose here that ciliopathies can be considered systemically as specific perturbations in a versatile dynamically regulated multifunctional molecular machine. Mainly based on the comprehensive description of the ciliary interactome, quantitative functional assays as well as human genetic data derived from ciliopathy patients, we will generate a comprehensive stream of content-rich quantitative data towards systemic analysis of ciliar function. These data will be used to generate and validate discrete models that describe functional modules and regulatory circuits in the ciliome as well as predicting biological context specific features of cilia as well as perturbations leading to ciliopathies. This will enable us to 1) understand the systemic features of discrete ciliary functions, 2) scrutinize the molecular disease mechanisms of different overlapping ciliopathies, and 3) develop therapeutic strategies towards improved treatment.

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