Aptamer probes for Epigenetic Peptide Targets

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DESCRIPTION (provided by applicant): Epigenetic aberrations underlie the pathogenesis of a number of human diseases that lack clear genetic alterations. For example, mental health diseases such as bipolar disorder and schizophrenia are associated with epigenetic changes in the promoters of enzymes that metabolize neurotransmitters. Other diseases in which epigenetic factors have been shown to play a role include cancer, autism, asthma and reproductive diseases. Gene expression differences in aging monozygotic twins suggest that epigenetic drift may be associated with chronic diseases that appear as we age. One of the most promising aspects of epigenomic research is that, unlike genetic aberrations, epigenetic aberrations are potentially reversible, by modulating the activities of the enzymes that stabilize or remodel specific chromatin states. In this project a set of epigenetic peptide and protein targets will be screened against libraries of nucleic acids using OrthoSystems new and highly successful approach, High Throughput Screening of Aptamers (HTSA), for discovery of DNA/RNA molecules that bind proteins with high affinity and specificity. HTSA aptamer hits will be investigated under standard experimental conditions for sensitivity, cross reactivity and robustness. In Phase II, aptamers that meet or exceed our performance standards will be made available to the re- search community through NIH reagent repositories (limited offering) or for a fee from OrthoSystems, Inc (full product line with attachment chemistry.) These aptamer products will serve as low cost, renewable, standar- dized affinity reagents for epigenomic research. This collaborative project will be led by OrthoSystems, Inc. with a subcontract to Syracuse University. PUBLIC HEALTH RELEVANCE: Epigenetic aberrations underlie the pathogenesis of mental health diseases, such as bipolar disorder and schizophrenia, by causing changes in the regulation of genes that produce enzymes to metabolize neuro transmitter molecules. Other diseases in which epigenetic factors play a role include cancer, autism, asthma and reproductive diseases, and may also be associated with chronic diseases that appear as we age. Many proteins are known to have critical roles in the manner in which DNA is packed tightly into chromo- somes or is available for expression of genes. This project will provide new and far more effective tools to measure the degree to which these proteins are modified. Unlike genetic aberrations, epigenetic changes are potentially reversible by modulating the activities of the enzymes that stabilize or remodel the packing of DNA in chromosomes.