Abnormalities in neuronal circuits within frontal cortex, striatum, thalamus and amygdala represent a major component of the pathophysiologic state of schizophrenia. The identification of the molecular mechanisms of antipsychotic drugs has been greatly impaired by the impossibility of studying specific neuronal populations. This Conte Center proposes to address this issue by using a novel technology that precisely allows the analysis of individual types of neurons that are intricately mixed and anatomically indistinguishable. This multidisciplinary approach involves a number of repetitive tasks that can be efficiently conducted in a centralized structure such as a Core. Over the past 20 years, considerable experience has been acquired in the Greengard laboratory with the operation of such a facility. An important aspect of the Core will be to support the characterization of novel candidate genes identified. Such responsibilities will include the production and maintenance of key reagents stocks, the development of new reagents, and the performance of routine tasks.
Specific Aims i nclude: I. The generation, production, purification and characterization of polyclonal/monoclonal antibodies, including phosphorylation state-specific antibodies. The Core will support the entire program by generating various polyclonal and monoclonal antibodies. In addition, phospho-specific antibodies against key signaling molecules will be produced, tested, and purified as needed. II. The engineering and production of viral reagents required by Projects 1-5. The Core will design and generate the necessary AAV viral reagents in order to drive specific expression of siRNAs or protein overexpression in mouse lines that express the Cre recombinase in specific cell populations. III. The performance of routine tasks. This will include the preparation, purification and characterization of various kinases, phosphatases, and intracellular signaling molecules. The Core will perform, where needed, yeast two-hybrid studies. The Core personnel has also extensive experience in various other routine tasks such as cell culture preparation, immunofluorescence techniques, siRNA design and testing.
to public health: Schizophrenia is a debilitating psychiatric disorder affecting ~1 % of the population. New therapeutic treatments for schizophrenia are needed. The Molecular &Biochemical Core will provide a common stock of the antibodies and reagents necessary for the work of all the Projects in this Conte Center Grant.
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