Integration of resources and studies to elucidate neuropeptide signaling

描述(申请人提供)：整合资源和研究以阐明神经肽信号转导摘要阐明药物成瘾的机制需要了解神经肽在神经网络中的作用。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，其他药物似乎介导了多肽反应。NIDA有着支持基础神经科学研究的悠久传统，这些研究导致了信号系统的阐明，并提供了对物质滥用和行为的批判性见解。信号肽已经使用了广泛的技术和模型生物进行了研究。多个互补的神经肽储存库以及多肽和转录实验现在都是可用的。即使有了这样的信息，挑战仍然是对神经肽及其与药物升级和滥用的关联的全面和系统的了解。我们建议通过开发研究社区迫切需要的公共和全面的神经肽资源来应对这一挑战，并通过集体分析蛋白质组和转录组实验来增强对基础神经科学和应用物质滥用水平上的细胞外信号肽的理解。为了实现这些目标，我们计划(目标1)整合互补多肽储存库并开发工具来组装和有效查询全面的公共实验资源和电子预测资源；(目标2)对可用的高蛋白质组学实验进行二次和联合分析；以及(目标3)进行蛋白质组和转录组实验的综合分析。总体战略是整合数据库、实验和平台上的互补信息，以提供对动态神经肽补体的独特和全面的理解。该项目的成果将是资源、工具和信息，这些资源、工具和信息将填补细胞间信号系统知识的重大空白，并为预防、诊断和治疗药物滥用提出目标。 公共卫生相关性：神经肽是信号肽，既影响药物滥用，也受到药物滥用和复杂行为的影响。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现有实验的信息，加强了NIDA对推进神经肽和药物滥用研究的重大贡献。拟议工作的结果将促进神经肽的识别和表征，这些神经肽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.