Characterization of Crustacean Innate Immune Response

对动物免疫学的广泛理解需要了解来自不同进化谱系的物种中专门的免疫相关分子的多样性。对于先天免疫反应尤其如此，这是脊椎动物和无脊椎动物共有的基本免疫过程。然而，我们目前对先天免疫的理解集中在模式生物上，如人类和小鼠；在这些生物中，存在着广泛的基因组资源。我们对非模式物种先天免疫反应的广度和范围的了解一直受到我们无法使用高通量基因组方法的限制。基因组测序技术的最新进展使得在非模式生物中全面检查和发现免疫相关转录本成为可能。新的免疫分子的发现将需要病原体挑战实验，伴随着差异表达和生物信息学分析，以及直接的功能分析，以全面确定生物功能。*节肢动物门包括地球上最丰富和生物上最成功的动物；海洋由不同种类的甲壳类动物主导。无脊椎动物的比较天然免疫学主要集中在陆栖无脊椎动物，如果蝇。这给我们的甲壳类免疫学知识留下了很大的空白。甲壳动物免疫学的传统方法依赖于光学和电子显微镜方法。高通量测序方法的应用为极大地扩展我们对无脊椎动物免疫学的理解带来了巨大的希望。*我最近获得了美国龙虾(Homarus Americanus)在病原体和环境压力挑战下的多个转录本，以及几个甲壳类物种的转录本，这些物种与美洲龙虾有共同的栖息地。这些转录资源为在生物信息学和功能水平上检验比较免疫学提供了令人兴奋的基础。*我的研究计划的长期目标是了解甲壳类动物先天免疫的能力和机制。我对这个提议有三个主要目的：*目的1.确定模式识别受体、Toll样受体和免疫缺陷细胞内信号分子和抗菌肽在十足类甲壳类动物中的保守性和多样性。*目的2.发现与细菌感染相关的美洲龙虾(Homarus Americanus)基因并对其进行功能注释。*目的3.表征抗菌肽对一组海洋甲壳类特定病原体和机会性病原体的生物活性。*这些研究将拓宽我们对美洲恒河猴天然免疫的生理机制的理解，以及更广泛的无脊椎动物免疫学。

A broad understanding of animal immunology requires understanding the diversity of specialized immune-related molecules in species from diverse evolutionary linages. This is especially true for innate immune responses which are fundamental immunological processes shared by vertebrate and invertebrate animals. However, our current understanding of innate immunity is focused on model organisms such as humans and mice; where extensive genomic resources exist. Our understanding of the breadth and scope of innate immune responses in non-model species has been limited by our inability to use high-through genomic approaches. Recent advances in genomic sequencing technology permit the comprehensive examination and discovery of immune-related transcripts in non-model organisms. Novel immune molecule discovery will require pathogen challenge experiments accompanied by differential expression and bioinformatic analysis and directed functional assays to comprehensively assign biological function.***The Arthropoda phylum encompasses the most abundant and biologically successful animals on earth; with the oceans dominated by diverse species of crustaceans. Comparative innate immunology in invertebrates has largely focused on terrestrial invertebrates such as Drosophila spp. This has left major gaps in our knowledge of crustacean immunology. Traditional approaches to crustacean immunology relied on light and electron microscopy approaches. The application of high-throughput sequencing approaches holds great promise for significantly expanding our understanding of invertebrate immunology.***I have recently generated multiple transcriptomes of the American lobster (Homarus americanus) under pathogen and environmental stress challenges; as well as transcriptomes from several crustacean species which share habitats with H. americanus. These transcriptomic resources represent an exciting basis for examining comparative immunology at both the bioinformatic and functional level. ***The long-term goals of my research program focus on understanding the capabilities and mechanisms underlying crustacean innate immunity. I have three major objectives for this proposal:***Objective 1. To determine the conservation and diversity of pattern recognition receptors, Toll-like receptor and Immunodeficiency intracellular signaling molecules and antimicrobial peptides among decapod crustaceans. ***Objective 2. To discover and functionally annotate American lobster (Homarus americanus) genes involved in responding to bacterial infection. ***Objective 3. To characterize the bioactivity of antimicrobial peptides against a panel of specific and opportunistic pathogens of marine crustaceans.***These studies will broaden our understanding of the physiological mechanisms underlying Homarus americanus innate immunity specifically, and invertebrate immunology more broadly.*****