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
Project partner
