(provide by applicant) The Cellular Signaling Core will provide research support for each of the three research projects supported by the Center. It provides a diverse array of serologic and cellular test parameters and expertise that are available for use to all scientists on the project. The technologies available include a variety of analytical markers such as highly sensitive ELISA and FACScan for neurotrophins, neuropeptides and cytokine determinations, immunohisto-chemistry, protein array, and molecular analysis of tyrosine kinase usage. Specifically, the investigators will provide the analytical support to test hypotheses regarding the association of known xenobiotic immunotoxicants and neurotoxicants as well as biologic agents, such as are found in the MMR vaccine, with autism. This core will be directed towards a thorough analysis of all aspects of the humoral and cellular immune system of patients with autism, and the interaction of these systems with neuronal cells. Particular attention will be paid to the hypothesis that autism has an autoimmune component. Blood samples shipped overnight express from the clinical assessment unit of Research Project I will be processed immediately for cell activation studies and a 2 ml sample coded and sent (frozen) to Core I for analytical profiling. The laboratory will have a support function in providing all aspects of immunological analysis for the research projects including cell culture and antigenic stimulation, interpretation of tissue staining and tyrosine and serine/threonine kinase receptor analysis in the human and animal systems. It will have a direct role in the development of a protein array system to be used by Projects II and III. Finally it will also have a role in advising the project scientists on any aspects of immune function, cell biology and the handling of tissue and serum samples. Once Project I is in full operation it is anticipated that 400 samples per year will be collected and sent to Core II. The ELISA screening used for objective IA (neurotrophins/ neuropeptides) and objective IIA (cytokines) will initially analyze 400 samples (140 autistic, 140 mentally retarded but not autistic, and 120 control) a number easily accommodated by the core. For analysis of autoantibodies, the goal is to initially analyze sera from 200 children (70 autistic, 70 mentally retarded but not autistic and 60 control) in the first year (tier 1 and tier 2 analyses). The additional samples will be banked for future studies. Thus Core II will process all biological samples in conjunction with overall coordination of the Administrative Core, to assure coordinated dissemination and banking samples in a timely manner.
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