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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）：使用锥形蜗牛C.泡状的海洋蜗牛，芋螺是一种鱼类捕食者，必须迅速捕食猎物。这是通过向猎物注射致命的芋螺肽毒液混合物来实现的，这些毒液是富含半胱氨酸的小肽，每种肽都对不同的配体或电压门控离子通道具有高亲和力。在过去的十年中，锥毒液已被证明是研究脊椎动物神经传递不可或缺的试剂，FDA已批准一种用于治疗慢性疼痛。我们有充分的理由相信，锥螺总体上仍然拥有大量具有药理学意义的未表征毒液（<100，000）。锥形肽还经历许多不寻常的翻译后修饰，这些修饰是由本身具有药理学意义的酶进行的。这种毒液成熟过程的特征很差。不幸的是，今天的锥毒液研究受到缺乏重要基因组资源的阻碍。因此，本申请的目的是（1）获得用于芋螺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）用于这些新毒液及其翻译后修饰中涉及的酶的功能表征。. 公共卫生相关性：该项目将使用高容量DNA和RNA测序来识别和表征锥形蜗牛中的新毒液基因。这一点很重要，因为这些毒液可用于脊椎动物神经生物学研究，并可作为控制慢性疼痛的药物。因此，发现和鉴定更多的锥毒液将促进基础研究和人类健康。