Exploring the Venom Repertoire of Parasitoids

探索寄生蜂的毒液

• 批准号: 8518396
• 负责人: JOHN Haynes WERREN
• 金额: $ 26.09万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8518396
• 关键词: Affect; Animals; Apoptosis; Basic Science; Behavior; Biological; Biological Assay; Biological Process; Biological Testing; Butterflies; Cell Culture Techniques; Cells; Data; Detection; Development; Drug Compounding; Evolution; Family; Future; Gene Expression; Gene Expression Profile; Genes; Genetic; Genomics; Gland; Goals; Human; Human Cell Line; Immunity; Individual; Insecta; Investigation; Larva; Life; Lipids; Medical; Medical Research; Medicine; Methods; Modeling; Order Coleoptera; Paralysed; Pathway interactions; Peptides; Pharmacopoeias; Physiological; Physiology; Process; Production; Prostate; Protein Biochemistry; Proteins; Proteome; Proteomics; Pupa; RNA Interference; Research; Resources; Staging; Stretching; Taxon; Testing; Therapeutic Agents; Time; Venoms; Wasp Venoms; Wasps; Work; base; cell type; cellular targeting; drug discovery; egg; flesh fly; fly; in vivo; multidisciplinary; neuroblast; novel; preference; protein expression; protein function; protein metabolite

DESCRIPTION (provided by applicant): Parasitoid wasps are abundant free-living insects that inject venom into and then lay their eggs on other insects. Parasitoids vary in hosts they utilize (flies, beetles, butterflies, etc), the life stage they parasitize (eggs, larvae, pupae), and whether their eggs are laid and develop within or outside the host. Due to this diversity, parasitoid venoms have evolved different mechanisms for manipulating host immunity, physiology and behavior in ways that enhance development of the parasitoid young. Among their effects, venoms can induce temporary or permanent paralysis, selective apoptosis, and alterations in host lipid physiology, immunity, and behavior. Yet virtually nothing is known about the diversity or function of individual parasitoid venom proteins. There are over 150,000 species of parasitoids. The model parasitoid Nasonia vitripennis alone has at least 79 different venom genes, of which 24 have no sequence similarity to any known proteins and contain no known conserved domains. Given their incredible number and diversity, parasitoids venoms represent an immense and untapped potential resource for drug discovery. The challenge is to efficiently assess this immense potential pharmacopeia for molecules with medical and research applications. Small biologically active peptides are particularly promising as therapeutic agents, and therefore their detection in parasitoid venoms is an important goal. We predict that evolutionary conservation in novel venom proteins can be used to identify short peptides with biological activity of relevance to medicine and research. If correct, this approach could rapidly accelerate new drug discovery among the immense pool of parasitoid venom proteins. Here we propose to investigate (a) the effects of individual Nasonia venom proteins in the whole animal Sarcophaga bullata (flesh fly) and in human cell lines by transcriptome, proteome, and physiological profiling, (b) assess the diversity of evolution of parasitoid venoms and identify conserved short peptides, and (c) test the hypothesis that evolutionary conservation can be used to predict short bioactive peptides, using our whole animal and human cell line assays. The project combines genetic, proteomic, physiological and evolutionary approaches to explore function, diversity, and potential for drug discovery in the immense pool of parasitoid venom proteins.

描述（由申请人提供）：寄生蜂是大量的自由生活的昆虫，它们将毒液注入其他昆虫，然后在其他昆虫身上产卵。寄生蜂在它们利用的宿主（苍蝇、甲虫、蝴蝶等）、它们寄生的生命阶段（卵、幼虫、蛹）以及它们的卵是在宿主内还是在宿主外产卵和发育方面各不相同。由于这种多样性，寄生蜂毒液已经进化出不同的机制来操纵宿主的免疫、生理和行为，从而促进寄生蜂幼蜂的发育。在它们的影响中，毒液可以诱导暂时或永久性瘫痪，选择性细胞凋亡，以及宿主脂质生理学，免疫和行为的改变。然而，实际上对单个寄生蜂毒液蛋白的多样性或功能一无所知。有超过150，000种寄生虫。仅模式寄生蜂丽蝇蛹集蜂（Nasonia vitripennis）就有至少79个不同的毒液基因，其中24个与任何已知蛋白质都没有序列相似性，也不含已知的保守结构域。鉴于其令人难以置信的数量和多样性，寄生蜂毒液代表了药物发现的巨大和未开发的潜在资源。目前的挑战是有效地评估这一巨大的潜在药典分子与医疗和研究应用。小的生物活性肽作为治疗剂是特别有前途的，因此它们在寄生蜂毒液中的检测是一个重要的目标。我们预测，新的毒液蛋白质的进化保守性可用于鉴定具有与医学和研究相关的生物活性的短肽。如果正确的话，这种方法可以在巨大的寄生虫毒液蛋白库中迅速加速新药的发现。在这里，我们建议调查（a）在整个动物Sarcophaga bullata的影响，单个纳苏尼亚毒液蛋白（b）通过转录组、蛋白质组和生理学特征分析，（B）评估寄生蜂毒液进化的多样性并鉴定保守的短肽，和（c）检验进化保守性可用于预测短生物活性肽的假设，使用我们的整个动物和人类细胞系分析。该项目结合了遗传学，蛋白质组学，生理学和进化方法，以探索寄生虫毒液蛋白巨大库中的功能，多样性和药物发现潜力。