Genomics-based Venom Studies Using the Cone Snail C. Bullatus

使用锥形蜗牛 C. Bullatus 进行基于基因组学的毒液研究

基本信息

批准号：
8219706
负责人：
Mark Douglas Yandell
金额：
$ 28.41万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-13 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8219706
关键词：
Acetylcholine Affinity Basic Science Budgets Cell Culture Techniques Complementary DNA Complex Conus genus Cultured Cells Cysteine DNA Sequence Data Distal Drug Controls Duct (organ) structure Elan brand of omega-conopeptide MVIIA Enzyme Gene Enzymes Evolution FDA approved Fishes Funding Gated Ion Channel Gene Expression Profile Genes Genome Genomics Goals Hand Health Human Insecta Length Libraries Ligands Light Marines Methods Neurobiology Neurologic Oocytes Peptides Pharmaceutical Preparations Phase Post-Translational Protein Processing Potassium Channel Process Production Proteins RNA Sequences Reading Reagent Regulation Research Resources Retinal Cone S Phase Salivary Glands Sampling Sequence Analysis Shotguns Snail Venoms Snails Sodium Channel Solid Techniques Tissues Toxin Transcript Universities Utah Venoms Work Xenopus laevis base chemical synthesis chronic pain cost cost effective falls follow-up genome sequencing innovation interest large scale production neurotransmission novel scaffold voltage ziconotide

项目摘要

DESCRIPTION (provided by applicant): Genomics-based venom studies using the cone snail C. bullatus. The marine snail, Conus bullatus is a fish predator and must quickly immobilize its prey. This is accomplished by injecting prey with a lethal cocktail of conopeptide venoms, small cysteine-rich peptides, each with a high affinity to a different ligand or voltage- gated ion channel. Over the last decade, cone venoms have proven indispensable reagents for the study of vertebrate neurotransmission, and the FDA has approved one for the treatment of chronic pain. There is good reason to believe that collectively the cone snails still harbor a large repertoire of uncharacterized venoms (<100,000) of pharmacological interest. Conopeptides also undergo many unusual posttranslational modifications, carried out by enzymes that are themselves of pharmacological interest. This process of venom maturation is poorly characterized. Unfortunately, cone venom research today is hindered by a lack of significant genomic resources. Hence, the purpose this application is (1) to obtain funds for Conus transcriptome and genome sequencing and analyses to identify new venoms and their posttranslational modifiers, and (2) for functional characterizations of these new venoms and the enzymes involved in their posttranslational modifications. . PUBLIC HEALTH RELEVANCE: This project will use high-volume DNA and RNA sequencing to identify and characterize new venom genes in cone snails. This is important because these venoms are useful for vertebrate neurobiology research and as drugs for control of chronic pain. Discovering and characterizing more cone venoms will thus further both basic research and human health.

描述（由申请人提供）：基于基因组学的毒液研究，使用锥形蜗牛C. bullatus。海洋蜗牛，康努斯·布拉图斯（Conus Bullatus）是一种鱼类捕食者，必须迅速固定猎物。这是通过将猎物注入致命的蛋白毒液，富含半胱氨酸的肽的致命鸡尾酒来实现，每种肽与不同的配体或电压离子离子通道具有很高的亲和力。在过去的十年中，锥体毒液已被证明是对脊椎动物神经传递研究的必不可少的试剂，FDA已批准一种用于治疗慢性疼痛的方法。有充分的理由相信，锥形蜗牛仍然具有大量未表征的毒液（<100,000）的药理学兴趣。综合肽还经历了许多具有药理学兴趣的酶进行的许多不寻常的翻译后修饰。毒液成熟过程的特征很差。不幸的是，今天缺乏大量的基因组资源来阻碍今天的锥毒研究。因此，该应用的目的是（1）获得用于圆锥转录组和基因组测序和分析的资金，以鉴定新的毒液及其翻译后修饰剂，以及（2）这些新毒液的功能特征以及参与其后转移修饰的酶。。公共卫生相关性：该项目将使用大量DNA和RNA测序来识别和表征锥蜗牛中新的毒液基因。这很重要，因为这些毒液可用于脊椎动物神经生物学研究，作为控制慢性疼痛的药物。因此，发现和表征更多的锥毒将进一步进一步基础研究和人类健康。