Integration of resources and studies to elucidate neuropeptide signaling

描述（由申请人提供）：整合资源和研究，以阐明神经肽信号传导摘要阐明药物成瘾的机制需要了解神经肽在神经元网络中的作用。这些信号肽介导对环境刺激的反应并影响成瘾行为。许多滥用药物直接与神经肽受体相互作用，其他药物似乎介导肽反应。NIDA在支持基础神经科学研究方面有着悠久的传统，这些研究导致了信号系统的阐明，并为药物滥用和行为提供了重要的见解。信号肽已经使用广泛的技术和模式生物进行了研究。多个互补的神经肽库和肽组学和转录组学实验现在可用。即使有这样的信息，挑战仍然是获得一个完整的和系统的了解神经肽组及其与药物升级和滥用的关联。我们建议通过开发研究界急需的公共和全面的神经肽资源，并通过集体分析蛋白质组学和转录组学实验来解决这一挑战，以增强对细胞外信号肽在基础神经科学和应用物质滥用水平的理解。为了实现这些目标，我们计划（目标1）整合互补肽库和开发工具，以组装和有效地查询实验和计算机预测的综合性和公共资源;挖掘此资源（目标2）进行二级和联合分析可用的高蛋白质组学实验;和（目标3）进行蛋白质组学和转录组学实验的综合分析。总体战略是整合跨数据库，实验和平台的互补信息，以提供对动态神经肽补体的独特而全面的理解。该项目的成果将是资源、工具和信息，将填补细胞间信号系统知识方面的关键空白，并为药物滥用的预防、诊断和治疗提出目标。 公共卫生相关性：神经肽是影响药物滥用和复杂行为的信号肽。拟议的项目通过开发公共生物信息资源以及整合和进一步挖掘已有实验的信息，加强了NIDA对神经肽和药物滥用研究进步的重大贡献。拟议工作的结果将促进神经肽的鉴定和表征，以支持与药物滥用相关的疾病的预后、诊断和治疗。

DESCRIPTION (provided by applicant): Integration of resources and studies to elucidate neuropeptide signaling Abstract Elucidating the mechanisms governing drug addiction requires knowledge of the role of neuropeptides on the neuronal networks. These signaling peptides mediate responses to environmental stimuli and influence addiction behaviors. Many drugs of abuse directly interact with neuropeptide receptors, and others appear to mediate peptide responses. NIDA has a long tradition of supporting fundamental neuroscience research that has lead to the elucidation of signaling systems and provided critical insights into substance abuse and behavior. Signaling peptides have been studied using a wide range of techniques and model organisms. Multiple complementary neuropeptide repositories and peptidomic and transcriptomic experiments are now available. Even with such information, the challenge remains to gain a complete and systematic understanding of the neuropeptidome and its association with drug escalation and abuse. We propose to address this challenge by developing a public and comprehensive neuropeptide resource much needed by the research community and by collectively analyzing proteomic and transcriptomic experiments to augment the understanding of extracellular signaling peptides both at the fundamental neuroscience as well as the applied substance abuse levels. To accomplish these objectives, we plan to (Aim 1) integrate complementary peptide repositories and develop tools to assemble and effectively query a comprehensive and public resource of experimental and in silico predictions; mine this resource to (Aim 2) perform secondary and joint analysis of available high proteomic experiments; and (Aim 3) perform integrated analysis of proteomic and transcriptomic experiments. The overarching strategy is to integrate complementary information across databases, experiments and platforms to provide a unique and comprehensive understanding of the dynamic neuropeptide complement. The outcome of this project will be resources, tools and information that will fill critical gaps in the knowledge on intercellular signaling systems and suggest targets for prevention, diagnosis and cure of substance abuse. PUBLIC HEALTH RELEVANCE: Neuropeptides are signaling peptides that both influence and are influenced by drug abuse and complex behaviors. The proposed project strengthens the significant contributions of NIDA to the advancement of neuropeptide and drug abuse research by developing public bioinformatic resources and by integrating and further mining information from experiments already available. Outcomes from the proposed work will advance the identification and characterization of neuropeptide that support the prognostic, diagnostic and treatment of disorders associated with substance abuse.