Aptamer probes for Epigenetic Peptide Targets

描述（由申请人提供）： 表观遗传畸变是许多缺乏明确遗传改变的人类疾病发病机制的基础。例如，双相情感障碍和精神分裂症等精神健康疾病与代谢神经递质的酶的启动子的表观遗传变化有关。表观遗传因素已被证明发挥作用的其他疾病包括癌症、自闭症、哮喘和生殖疾病。单卵双胞胎基因表达的差异表明，表观遗传漂变可能与随着年龄的增长而出现的慢性疾病有关。表观基因组研究最有前途的方面之一是，与遗传畸变不同，表观遗传畸变是潜在可逆的，通过调节稳定或重塑特定染色质状态的酶的活性。 在这个项目中，一组表观遗传肽和蛋白质靶点将使用OrthoSystems新的和非常成功的方法，适体高通量筛选（HTSA），针对核酸文库进行筛选，以发现以高亲和力和特异性结合蛋白质的DNA/RNA分子。将在标准实验条件下研究HTSA适体命中的灵敏度、交叉反应性和稳健性。在第二阶段，符合或超过我们性能标准的适体将通过NIH试剂库（有限供应）或从OrthoSystems，Inc（含附件化学的完整产品线）收费提供给研究界。这些适体产物将作为低成本、可再生、标准化的亲和试剂用于表观基因组研究。该合作项目将由OrthoSystems，Inc.领导。在锡拉丘兹大学读书。 公共卫生相关性： 表观遗传畸变是双相情感障碍和精神分裂症等精神健康疾病发病机制的基础，它引起产生酶以代谢神经递质分子的基因调节的变化。表观遗传因素发挥作用的其他疾病包括癌症，自闭症，哮喘和生殖疾病，也可能与随着年龄增长而出现的慢性疾病有关。已知许多蛋白质在DNA被紧密包装到染色体中或可用于基因表达的方式中具有关键作用。该项目将提供新的和更有效的工具来测量这些蛋白质被修饰的程度。与遗传畸变不同，表观遗传变化通过调节稳定或重塑染色体中DNA包装的酶的活性而具有潜在的可逆性。

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.