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.

项目概要：Molecular Tools Core 这项BRAIN Initiative建议的主要特点之一是“催产素对神经回路的调节 功能和行为”是分子工具研究支持的核心。每个项目小组都在检查 催产素释放和催产素受体信号传导的作用。催产素是肽类激素中的典型 和神经调节剂，已经以各种形式研究了超过世纪，并且具有明确的生理作用， 行为相关性和生物医学重要性。然而，人们对细胞和网络效应知之甚少 催产素信号。这部分是由于缺乏特异性抗体来确定哪些大脑区域和细胞 型表达催产素受体，以及其他分子工具，专门操纵和监测 高时空精度的催产素信号传导。我们的实验室已经生成，验证，并正在分发 第一个针对小鼠催产素受体的特异性抗体，也开发了第一个成功的版本。 笼状催产素化合物。鉴于科学界的成功使用和热情， 由于需要继续验证和优化，我们感到有必要扩大这些试剂的生产规模 并改善其功能。显然，对这些资源有着迫切和广泛的需求， 由核心设施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， 这些抗体广泛地应用，并优化它们的效用和特异性，包括产生单克隆抗体。 目的2是产生和优化缩宫素受体激动剂的笼状和光开关形式， 拮抗剂，可用于特异性描绘催产素受体信号传导作用于何时何地产生 中枢神经系统和外周组织的生理反应。Aim 3生成试剂， 点击化学涉及标记催产素，以可视化催产素在固定和活组织，以帮助确定是否 以及外源性催产素递送在生物体内起作用的情况。目标4是在需要时生成有用的 开发新的小鼠品系，用于催产素能信号传导的细胞类型特异性解剖，并利用 转录组数据和其他基因表达资源，以促进对分子定义的 社会空间行为中的Oxt+和Oxtr+人群。