BIOCHEMICAL ISOLATION OF PEPTIDES: ROLE IN MENTAL HEALTH

描述（来自申请人摘要）：通过C-末端相关的肽 FLRFamide影响行为，包括惊恐发作和焦虑。因此，在本发明中， FLRF酰胺肽信号转导的扰动可能导致异常的精神状态， 活动虽然FLRF酰胺肽在精神健康中发挥作用，但它们的位点 合成、表达调控和转导机制并不 知道的已经分离出许多FLRF酰胺肽，但是没有FLRF酰胺肽。 肽和基因已经从遗传上易驯服的哺乳动物中鉴定出来。因此，在本发明中， 提出的目标是分离小鼠FLRF酰胺并描述其在以下方面的作用： 哺乳动物生理学 所提出的假设是FLRF酰胺肽存在于小鼠、人类和哺乳动物中。 模型系统适用于分子遗传学研究，并且肽 在行为中起着关键作用。所提出的假设得到了 如下：1）分离小鼠FLRF酰胺肽，2）FLRF酰胺的存在 哺乳动物脑中的免疫活性，和3）结构和功能 脊椎动物和无脊椎动物肽之间的同源性。校长 研究者将以下列目的检验该假设：1）分离a 小鼠FLRF酰胺肽，2）克隆小鼠FLRF酰胺cDNA和基因，和3） 确定小鼠FLRF酰胺肽的分布。研究者将 通过以下方式实现这些目的：1）从FLRF酰胺中纯化FLRF酰胺免疫反应性材料， 小鼠脑匀浆，2）扩增来自小鼠脑的FLRF酰胺转录物 mRNA和筛选小鼠基因组文库，和3）产生针对该mRNA的抗血清。 小鼠FLRF酰胺肽。 实现这些目标对于跨学科的基础至关重要。 一项旨在解读FLRF酰胺在人体生理学中作用的研究。未来 研究将利用分子遗传学方法的力量， 基因敲除和转基因小鼠，建立生物测定，并分离相互作用 分子，以确认功能，阐明表达调控， 描绘信令。该研究为今后的研究提供了基础 FLRF酰胺激动剂和拮抗剂的设计，以及用于大规模筛选 药理学化合物和与人类健康相关的临床试验。

DESCRIPTION (from applicant's abstract): Peptides related by a C-terminal FLRFamide affect behavior, including panic attack and anxiety. Thus, perturbations in FLRF amide peptide signaling may lead to abnormal mental activity. Although FLRFamide peptides play a role in mental health, their sites of synthesis, regulation of expression and transduction mechanisms are not known. Numerous FLRFamide peptides have been isolated, however no FLRFamide peptide and gene has been identified from a genetically tractable mammal. Thus, the proposed goal is to isolate mouse FLRFamide and delineate its role in mammalian physiology. The proposed hypothesis is that an FLRFamide peptide exists in mouse, a human model system amenable to molecular genetics research, and that the peptide plays a critical role in behaviors. The proposed hypothesis is supported by the following: 1) isolate a mouse FLRFamide peptide, 2) the presence of FLRFamide immunoactivity in mammalian brain, and 3) the structural and functional homology between vertebrate and invertebrate peptides. The principal investigator will test the hypothesis with the following aims: 1) isolate a mouse FLRFamide peptide, 2) clone the mouse FLRFamide cDNA and gene, and 3) determine the distribution of the moue FLRFamide peptide. The investigator will achieve these aims by: 1) purifying an FLRFamide immunoreactive material from a mouse brain homogenate, 2) amplifying the FLRFamide transcript from mouse brain mRNA and screening a mouse genomic library, and 3) raising antisera to the mouse FLRFamide peptide. Accomplishing these aims is crucial to the foundation of the interdisciplinary study to decipher the role of FLRFamide in human physiology. The future research will utilize the power of a molecular genetics approach to generate knockouts and transgenic mice, establish bioassays, and isolate interactive molecules to confirm function, elucidate regulation of expression, and delineate signaling. The proposed research provides the basis of the future design of FLRFamide agonists and antagonists, and assays for mass screening of pharmacological compounds and clinical tests relevant to human health.