Molecular Tools Core

分子工具核心

• 批准号: 10705993
• 负责人: MOSES VICTOR CHAO
• 金额: $ 68.5万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10705993
• 关键词: Agonist; Antibodies; Area; BRAIN initiative; Behavior; Behavioral; Biochemistry; Brain; Central Nervous System; Chemistry; Communication; Communities; Core Facility; Data; Development; Dissection; Electron Microscopy; Elements; Ensure; Epitopes; Extramural Activities; Fc Receptor; Gene Expression; Generations; Genetic; Genetic Models; Goals; Hippocampus; Hypothalamic structure; In Vitro; Individual; Infusion procedures; International; Intranasal Administration; Letters; Ligands; Methods; Microtus; Molecular; Monitor; Monoclonal Antibodies; Mouse Cell Line; Mus; Neuromodulator; Neurons; Optics; Organism; Oxytocin; Oxytocin Receptor; Peptide Signal Sequences; Peptides; Peripheral; Physiological; Population; Postdoctoral Fellow; Production; Rattus; Reagent; Receptor Signaling; Research Support; Resources; Rodent; Role; Signal Transduction; Social Behavior; Songbirds; Spatial Behavior; Specificity; Study models; System; Testing; Tissues; Training; Validation; Venus; Viral; Visualization; Work; antagonist; blood-brain barrier crossing; cell type; genetic approach; improved; in vivo; innovation; loss of function; manufacturing scale-up; medical schools; member; mouse model; neural circuit; neuroregulation; novel; peptide hormone; receptor; response; sensor; spatiotemporal; tissue fixing; tool; transcriptome

Project Summary: Molecular Tools Core One of the major features of this BRAIN Initiative proposal on “Oxytocin Modulation of Neural Circuit Function and Behavior” is this Molecular Tools Research Support Core. Each of the Project teams is examining oxytocin release and the action of oxytocin receptor signaling. Oxytocin is exemplary among peptide hormones and neuromodulators, has been studied in various forms for over a century, and has clear physiological action, behavioral relevance, and biomedical importance. However, little is known about the cellular and network effects of oxytocin signaling. This is in part due to lack of specific antibodies for determining which brain areas and cell types express oxytocin receptors, as well as other molecular tools for specifically manipulating and monitoring oxytocin signaling with high spatiotemporal precision. Our labs have generated, validated, and are distributing the first specific antibodies to mouse oxytocin receptors, and have also developed the first successful versions of caged oxytocin compounds. Given the successful use and enthusiasm by the scientific community together with the need for continued validation and optimization, we feel obliged to scale-up production of these reagents and improve their functionality. There is clearly urgent and widespread need for these resources, which are best produced, tested, and distributed by a Core facility rather than by individual labs. Aim 1 of the Molecular Tools Core is to continue production of oxytocin receptor antibodies, distribute these antibodies broadly, and optimize their utility and specificity including generation of monoclonal antibodies. Aim 2 is to generate and optimize caged and photo-switchable forms of oxytocin receptor agonists and antagonists, useful for delineating specifically when and where oxytocin receptor signaling acts to generate physiological responses in the central nervous system and in peripheral tissues. Aim 3 generates reagents for click chemistry involving tagged oxytocin, to visualize oxytocin within fixed and live tissue, to help determine if and where exogenous oxytocin delivery acts within an organism. Aim 4 is to generate useful and when needed develop new mouse lines for cell-type specific dissection of oxytocinergic signaling, and to leverage transcriptome data and other gene expression resources to facilitate studies on the roles of molecularly defined Oxt+ and Oxtr+ populations in socio-spatial behavior.

项目总结：分子工具核心 这一脑部倡议提案的主要特点之一就是“催产素对神经回路的调制” 功能和行为“是这个分子工具研究支持的核心。每个项目团队都在检查 催产素释放和催产素受体信号的作用。催产素是多肽激素中的典范 和神经调节剂，已经以各种形式被研究了一个多世纪，并具有明确的生理作用， 行为相关性和生物医学重要性。然而，人们对蜂窝和网络的影响知之甚少 催产素信号。这在一定程度上是由于缺乏特定的抗体来确定哪些脑区和细胞 类型表达催产素受体，以及其他用于特定操作和监测的分子工具 催产素信号具有很高的时空精度。我们的实验室已经生成、验证并分发 第一个针对小鼠催产素受体的特异性抗体，并已经开发出第一个成功的版本 笼子里的催产素化合物。鉴于科学界的成功使用和热情 由于需要继续验证和优化，我们感到有义务扩大这些试剂的生产 并改进它们的功能。显然，迫切和广泛地需要这些资源，这些资源是最好的 由Core工厂而不是由单个实验室生产、测试和分发。 分子工具核心的目标1是继续生产催产素受体抗体，分发 这些抗体广泛，并优化其实用性和特异性，包括产生单抗。 目标2是产生和优化笼式和光可切换形式的催产素受体激动剂和 拮抗剂，用于具体描述催产素受体信号何时何地作用于 中枢神经系统和周围组织的生理反应。AIM 3为 单击涉及标记催产素的化学，以可视化固定和活组织中的催产素，以帮助确定 以及外源性催产素在生物体内的作用。目标4是在需要的时候生成有用的和 开发新的小鼠品系，用于催产素能信号的细胞型特异性分离，并利用 转录组数据和其他基因表达资源，促进分子定义的作用的研究 Oxt+和Oxtr+群体的社会空间行为。