Objectif
Mutations in about 400 different genes have been associated with Cognitive Disorders (CD), such as mental retardation, autism, neurodegenerative disorders, and psychiatric disorders. Whereas CD impose a major medical and socio-economical problem, there are no systematic studies that aim to provide insight into common mechanisms in CD. We propose a systems biology approach to gain insight into common mechanisms leading to cognitive impairment: (1) Identification of genes involved in cognitive disorders. Despite considerable progress in the identification of genes underlying CD, the majority of causative genes in CD remain unidentified. Therefore, our first objective is to identify new genes causative of CD by implementing high-throughput strategies. (2) Elucidation of molecular networks that are commonly disrupted in CD. Recent genetic and neurobiological research revealed evidence for a number of molecular and cellular pathways that are shared by the various genetic CDs. Prominent examples are Rho GTPase-related genes and genes that regulate chromatin structure/function (epigenetics) associated with mental retardation and autism. Our second objective is to systematically explore this concept by elucidation of molecular networks using functional genomics strategies in genetic models that are the cornerstone of neuroscience, such as mouse and fruit fly. (3) Identify genetic modifiers and small compounds that modulate the disease phenotype. Our third objective is to resolve the molecular underpinnings of the large degree of clinical variability that is typical for all types of CD, even among patients carrying identical gene mutations. Genetic modifier screens in cultured primary neurons as well as in available Drosophila models for CD will be used to reveal phenotypically relevant genetic interactions and molecular networks. Moreover, drug screens shall be conducted in fly and cellular models for CD, which will lead to pharmacological rescue of mouse models.
Champ scientifique
Appel à propositions
FP7-HEALTH-2009-two-stage
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Régime de financement
CP-IP - Large-scale integrating projectCoordinateur
6525 XZ Nijmegen
Pays-Bas
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Participants (14)
80539 Munchen
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75654 Paris
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1985713831 Tehran
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CB10 1SA SAFFRON WALDEN
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CB4 1GU Cambridge
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1030 Wien
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W1B 1AL LONDON
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67404 Illkirch Graffenstaden
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CB4 3PD Cambridge
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1050 Brussels
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54550 LAHORE 20
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EH8 9YL Edinburgh
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OX1 2JD Oxford
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3761HA SOEST
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