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

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芋螺肽毒液的致命鸡尾酒来实现的，芋螺肽毒液是富含半胱氨酸的小肽，每种肽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）。锥肽也经历许多不寻常的翻译后修饰，由本身具有药理学意义的酶进行。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。.

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. .