The Sp185/333 system in the sea urchin; gene family structure, gene regulation and protein function

众所周知，人类免疫系统产生大量多样性的抗体来防御病原体;产生这种多样性的机制也很清楚。虽然无脊椎动物不产生抗体，但它们也可以产生免疫多样性来应对感染;但这些机制仍然知之甚少。 这项工作的首要目标是了解一种无脊椎动物，加州紫海胆，通过产生多种非抗体蛋白质来抵御海洋中众多微生物的机制。 PI将研究海胆中的一个基因和蛋白质家族（Sp185/333基因家族），该家族对细菌感染的反应表现出高度的多样性。利用各种分子、生物化学和计算方法，PI将解决1）在这个非抗体基因家族中如何产生免疫多样性2）如何调节这个基因家族的表达以及3）因此产生的蛋白质如何实际起作用以保护动物免受病原体的侵害。拟议工作的结果将与其他动物（包括小鼠和人类）的免疫机制进行比较，了解不同的免疫系统如何保护宿主免受感染的多样性和广度。 了解海胆免疫多样化系统的功能可能有助于确定其他动物（如人类）是否采用类似的方法。 研究人员将利用这个机会培训各级学生，并建立和加强国际合作。 培训将包括制作一个基于网络的、可公开获取的生物信息学工具，以改进基因序列的组装和分析。 研究培训将导致出版物和演示文稿和本科生，研究生和博士后研究人员的研究培训。

It is well known that the human immune system generates a large diversity of antibodies to defend against pathogens; the mechanisms to generate that diversity are well understood. Although invertebrate animals do not make antibodies, they also can generate immune diversity in response to infection; but these mechanisms are still poorly understood. The overarching goal of this work is to understand the mechanisms that one invertebrate, the California purple sea urchin, employs to defend itself against the multitudes of microbes in the ocean by generating a diversity of non-antibody proteins. The PI will investigate one family of genes and proteins (the Sp185/333 gene family) in sea urchins that shows a high level of diversity in response to bacterial infection. Using a variety of molecular, biochemical and computational approaches, the PI will address 1) how immune diversity is generated within this non-antibody gene family 2) how expression of this family of genes is regulated and 3) how the proteins thus produced actually function to protect the animal from pathogens.Outcomes from the proposed work will be compared with immune mechanisms in other animals, including mice and humans, to understand the variety and breadth of how different immune systems protect hosts from infection. Understanding how the sea urchin immune diversification system functions may aid in determining whether other animals, such as humans, employ similar approaches. The investigators will use the opportunity for training all levels of students and to establish and strengthen international collaborations. Training will include the production of a web-based, publicly available bioinformatic tool for improved gene sequence assembly and analysis. Research training will lead to publications and presentations and research training for undergraduates, graduate students and postdoctoral investigators.