Objective
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.
Fields of science
Call for proposal
FP7-HEALTH-2009-two-stage
See other projects for this call
Funding Scheme
CP-IP - Large-scale integrating projectCoordinator
6525 XZ Nijmegen
Netherlands
See on map
Participants (14)
80539 Munchen
See on map
75654 Paris
See on map
1985713831 Tehran
See on map
Participation ended
CB10 1SA SAFFRON WALDEN
See on map
CB4 1GU Cambridge
See on map
1030 Wien
See on map
Participation ended
W1B 1AL LONDON
See on map
67404 Illkirch Graffenstaden
See on map
CB4 3PD Cambridge
See on map
Participation ended
1050 Brussels
See on map
54550 LAHORE 20
See on map
EH8 9YL Edinburgh
See on map
OX1 2JD Oxford
See on map
3761HA SOEST
See on map