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Multitasking anti-pathogen activities of the sea urchin SpTransformer protein family: insights into an evolutionarily divergent metazoan immune system

海胆 SpTransformer 蛋白家族的多任务抗病原体活性：深入了解进化上不同的后生动物免疫系统

基本信息

批准号：
1855747
负责人：
L Courtney Smith
金额：
$ 77.5万
依托单位：
George Washington University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-15 至 2024-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1855747&HistoricalAwards=false
关键词：
Multitasking anti pathogen activities sea

项目摘要

Sea water has lots of marine bacteria. So, how do animals (sea urchins) that live in sea water protect themselves against infections? Answers to this question apply to successful management of marine populations and productive aquaculture. The sea urchin immune system lacks important aspects that are present in humans. For example, sea urchins do not produce antibodies. Instead, they express a family of anti-pathogen proteins called Transformer proteins (they change shape!). At least one of the Transformer proteins acts very broadly, and can bind to bacteria, fungi, and other pathogens. This is very different from one antibody that binds only one target. The hypothesis is that each Transformer protein has a slightly different repertoire of targets, which gives sea urchins great flexibility to protect themselves against pathogens with similar, different, or overlapping targets. Because of the large variety of slightly different Transformer proteins, their complex anti-pathogen activities are likely essential for sea urchins to survive. This project integrates research with education in the following manner. Artistic illustrations of science are effective for communicating science to the general public. An Introductory Biology course will be designed and taught specifically for fine arts majors by faculty in Biology and the Arts. Artist/scientist collaborations can improve whether people learn and understand important concepts in science, which will aid in science literacy. Furthermore, improved science understanding by environmental policy students could have impacts on official government policy. Sea urchins have a complex and robust anti-pathogen innate immune system comprised, in part, of SpTransformer (SpTrf; formerly Sp185/333) proteins. The recombinant (r)SpTrf-E1 protein binds to Vibrio and yeast but not to Bacillus. It binds LPS, beta-1,3-glucan, and flagellin, but not peptidoglycan. rSpTrf-E1 is intrinsically disordered and transforms to alpha-helical in the presence of anionic targets such as PO4 groups. The investigators predict that other versions of SpTrf proteins act similarly but recognize different but overlapping targets. They will attempt to define the binding sites for rSpTrf-E1, define the targets bound by other rSpTrf proteins, determine whether other rSpTrf proteins undergo conformational transformation like (r)SpTrf-E1, and test the anti-pathogen activities of other SpTrf proteins in vitro and in vivo. Outcomes are expected to clarify the binding and structural characteristics of the SpTrf proteins and their activities in host defense, providing a unique example of immunological adaptations by a basal deuterostome. Art to illustrate science is an effective way for communicating science to the general public. However, art students generally do not learn much in standard introductory science courses. Hence, an Introductory Biology course will be designed and taught specifically for fine arts majors by faculty in Biology and the Arts. The art inspiration will be the science learned from lectures, discussions, and contact with scientists. Outcomes will highlight opportunities for artist/scientist collaborations such as improved data illustration, and for environmental science policy students to learn about important concepts in science, which may have impacts on official government policy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

海水中含有大量的海洋细菌。那么，生活在海水中的动物（海胆）如何保护自己免受感染呢？这个问题的答案适用于海洋种群和高产水产养殖的成功管理。海胆免疫系统缺乏人类所具有的重要方面。例如，海胆不产生抗体。相反，它们表达一个称为转化蛋白的抗病原体蛋白家族（它们会改变形状！）。至少一种转化蛋白的作用非常广泛，可以与细菌、真菌和其他病原体结合。这与仅结合一个靶标的一种抗体非常不同。假设每种转化蛋白的靶标都略有不同，这使海胆具有很大的灵活性，可以保护自己免受具有相似、不同或重叠靶标的病原体的侵害。由于转化蛋白种类繁多，略有不同，它们复杂的抗病原体活性可能对海胆的生存至关重要。该项目通过以下方式将研究与教育结合起来。科学的艺术插图对于向公众传播科学是有效的。生物学入门课程将由生物学和艺术学院的教师专门为美术专业设计和教授。艺术家/科学家的合作可以提高人们学习和理解重要科学概念的能力，这将有助于提高科学素养。此外，环境政策学生提高科学理解可能会对官方政府政策产生影响。海胆具有复杂而强大的抗病原体先天免疫系统，部分由 SpTransformer（SpTrf；以前的 Sp185/333）蛋白组成。重组 (r)SpTrf-E1 蛋白与弧菌和酵母结合，但不与芽孢杆菌结合。它结合 LPS、β-1,3-葡聚糖和鞭毛蛋白，但不结合肽聚糖。 rSpTrf-E1 本质上是无序的，并且在存在阴离子靶标（例如 PO4 基团）时转变为 α 螺旋。研究人员预测，其他版本的 SpTrf 蛋白的作用类似，但识别不同但重叠的目标。他们将尝试定义rSpTrf-E1的结合位点，定义其他rSpTrf蛋白结合的靶点，确定其他rSpTrf蛋白是否经历像(r)SpTrf-E1那样的构象转变，并测试其他SpTrf蛋白的体外和体内抗病原体活性。预计结果将阐明 SpTrf 蛋白的结合和结构特征及其在宿主防御中的活性，为基础后口动物的免疫适应提供一个独特的例子。用艺术阐释科学是向公众传播科学的有效方式。然而，艺术学生通常在标准的科学入门课程中学到的东西不多。因此，生物学入门课程将由生物学和艺术系的教师专门为美术专业设计和教授。艺术灵感将是从讲座、讨论和与科学家接触中学到的科学。成果将突出艺术家/科学家合作的机会，例如改进的数据说明，以及环境科学政策学生了解科学中的重要概念，这可能对官方政府政策产生影响。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。