Project: Multidisciplinary project investigating the neurobiology of chronic mental disease from single molecules to behavioral analysis in animal models

Our proposed research invokes a multidisciplinary approach to investigate mechanisms by which specific proteins are involved in the pathophysiology of chronic mental diseases (CMD), like schizophrenia and affective disorders. The premise underlying our multidisciplinary approach relies on complementary skills among the participants, allowing for a truly synergistic added-on value. Our research will combine novel and cutting-edge methodologies from biochemistry (conformer assays), proteomics (quantitative iTRAQ), cell biology (live cell imaging), animal model generation (in utero electroporesis) and behavioral analysis (episodic memory, in vivo microdialysis). We propose a novel bottom-up approach where translational value for clinical psychiatry is created through fundamental research on candidate proteins and corresponding animal models. Specifically, the expected results are likely to enable better understanding of the underlying molecular mechanisms of psychiatric diseases, will provide biological diagnostics and identify novel pharmacological targets. The research project involves five scientists with different expertises to elucidate the functions of the DISC1/NDEL1/centrosomal complex, a protein complex with an established link to CMD: Carsten Korth (Germany; protein biochemistry, molecular biology, neuropathology), Jesus Requena (Spain; biochemistry, structural biology, proteomics and mass spectrometry), Chiara Zurzolo (France; cell biology, live cell imaging, molecular biology), Joseph P. Huston (behavioral neuroscience, in vivo microdialysis), Orly Reiner (Israel; genetics, neuronal migration). The following scientific issues will be addressed: 1. Biochemistry and cell biology of insoluble and oligomeric proteins of the DISC1/NDEL1 complex proteins in cell and animal models of CMD. 2. Molecular and functional interactions of the DISC1/NDEL1 complex with neurotransmitters and neurotransmitter-related proteins, particularly dopamine, to characterize the link to the known neurotransmitter metabolism disturbances in CMD. 3. Generation of animal models reflecting subtle, aberrant corticogenesis and their behavioral analysis

Acronym DISCover
Duration 01/06/2010 - 31/05/2013
Network NEURON
Call NEURON-2009 New Technologies

Project partner

Number Name Role Country
1 Heinrich Heine University Düsseldorf Coordinator Germany
2 Heinrich Heine University Düsseldorf Partner Germany
3 Weizmann Institute of Science Partner Israel
4 University of Santiago de Compostela Partner Spain
5 Institut Pasteur Partner France