CAREER: Venom Evolution in Sicariid Spiders: A System for Undergraduate Training in Integrative Biology

职业：刀蜘蛛的毒液进化：综合生物学本科培训系统

• 批准号: 0546858
• 负责人: Greta Binford
• 金额: $ 64.39万
• 依托单位: Lewis and Clark College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0546858&HistoricalAwards=false
• 关键词: CAREER; Venom; Evolution; Sicariid; Spiders

Spider venoms are cocktails of chemicals evolutionarily designed for prey immobilization. Large differences in venom composition among the few studied species make the rest of the 39,000 species exciting sources of discovery of novel chemistry. Moreover, this chemical diversity makes a great context for studying evolutionary mechanisms that create novel toxins and modify them over time. This CAREER grant will fund development of an undergraduate-centered research program focused on the evolutionary origin and diversification of a unique and medically important toxin in venoms of brown recluse spiders and their relatives (Sicariidae). This toxin, sphingomyelinase D (SMase D) causes dermonecrotic lesions after bites of these spiders. The evolution of SMase D is particularly interesting because this enzyme is unique to venoms of sicariid spiders and pathogenic bacteria that cause disease in farm animals. Recent evidence from the PI and collaborators indicates that the evolutionary history of this toxin includes lateral transfer between spiders and bacteria. Furthermore, this toxin is a member of a gene family in spiders that undergoes periodic homogenization among different members, and either gene duplication and loss, or turning on and off of genes, which has resulted in loss of SMase D activity in some species.The specific research goals are to: (1) resolve relationships among worldwide representatives of species in this lineage and their close relatives using molecular phylogenetic analyses; (2) analyze the dynamics of origin and loss of venom-expressed SMase D using comparative enzyme assays and analyses of venom-expressed genes (cDNAs) from across the complete range of species with this toxin; (3) refine our understanding of the source of origin by probing for related genes in related groups of spiders. Understanding the mechanisms of origin and diversification of SMase D will serve as a case study of the molecular evolution of a unique toxin, and will provide information of medical relevance. Understanding the distribution and diversity of the SMase D molecule will inform us about the risks of bites from related species, and will aid in the development of treatments that are effective against bites of any member of this spider family. In so doing, it will promote awareness of the value of understanding basic systematics, organismal diversity, and evolution for the field of biological toxicology.Educational goals: This work will involve undergraduates in collaborative, interdisciplinary research that spans organisms and molecules. They will learn the value of approaching questions with an evolutionary (historical) perspective. In coursework, the PI will: (1) expand a phylogenetic biology course at Lewis & Clark College that includes bioinformatics, reconstruction of tree topologies and ancestral character states, and applications of these methods; (2) create a non-majors arachnology course that emphasizes the value of evolutionary approaches and integrated knowledge of organisms; (3) create a Web-based interactive diagnostic key for Loxosceles and Sicarius species diversity that is connected to the Tree of Life Web site.

蜘蛛毒液是用于捕食固定化的化学物质的鸡尾酒。少数研究物种的毒素成分差异很大，使39,000种新型化学发现的来源令人兴奋。此外，这种化学多样性是研究产生新型毒素并随着时间修改的进化机制的理想背景。这项职业赠款将资助以本科生为中心的研究计划的发展，该研究计划着重于棕色隐居蜘蛛及其亲戚（Sicariidae）的毒液中独特且具有医学重要的毒素的多样化。这种毒素，鞘磷脂酶D（Smase d）会在咬伤后引起皮肤分子病变。 Smase D的演变特别有趣，因为该酶是sicariid蜘蛛的毒液和引起农场动物疾病的致病细菌所特有的。 PI和合作者的最新证据表明，该毒素的进化史包括蜘蛛和细菌之间的横向转移。此外，这种毒素是蜘蛛中基因家族的成员，在不同成员之间经历周期性均质化，基因的重复和丧失和损失，或者打开基因，或者打开和关闭基因，这导致某些物种中Smase D活性的丧失。某些特定的研究目标是：（1）使用该层次的ph及其分析的分析及其分析的分析中的物种之间的关系。 （2）使用比较酶测定和分析毒液表达的基因（CDNA），分析毒素表达的基因（CDNA）的原点和丢失的动力学，并分析了这种毒素的完整物种范围； （3）通过探测相关蜘蛛相关基因的探测来源的理解。了解SMASE D的起源机制和多样化的机制将作为对独特毒素的分子演化的案例研究，并将提供医学相关性的信息。了解SMASE D分子的分布和多样性将告知我们相关物种叮咬的风险，并将有助于开发对抗咬菌家族的任何成员有效的治疗。通过这样做，它将提高人们对理解基本系统学，生物多样性和对生物毒理学领域的进化的价值的认识。教育目标：这项工作将涉及本科生在协作，跨学科研究中，跨越生物体和分子。他们将学习以进化（历史）观点来解决问题的价值。在课程中，PI将：（1）在Lewis＆Clark College上扩展系统发育生物学课程，其中包括生物信息学，树拓扑和祖先特征状态的重建以及这些方法的应用； （2）创建一个非放大的养殖课程，该课程强调进化方法的价值和对生物体的综合知识； （3）创建一个基于网络的互动诊断密钥，用于连接到生命之树网站的Loxosceles和Sicarius物种多样性。