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

描述（由申请人提供）：基于基因组学的锥螺C. bullatus毒液研究。海蜗牛，Conus bullatus是一种鱼类捕食者，必须迅速使猎物动弹不得。这是通过给猎物注射致命的康多肽毒液鸡尾酒来完成的，康多肽毒液是一种富含半胱氨酸的小肽，每一种都对不同的配体或电压门控离子通道具有高亲和力。在过去的十年里，锥体毒液已被证明是脊椎动物神经传递研究中不可或缺的试剂，美国食品和药物管理局（FDA）已批准一种用于治疗慢性疼痛。有充分的理由相信，总的来说，锥体蜗牛仍然拥有大量未表征的毒液（<100,000），具有药理意义。conop肽也经历了许多不寻常的翻译后修饰，这些修饰是由酶进行的，这些酶本身具有药理意义。毒液成熟的这一过程没有得到很好的描述。不幸的是，由于缺乏重要的基因组资源，今天的锥虫毒液研究受到阻碍。因此，本申请的目的是(1)为Conus转录组和基因组测序和分析获得资金，以鉴定新毒液及其翻译后修饰因子，以及(2)对这些新毒液及其翻译后修饰所涉及的酶进行功能表征。

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. .