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

海水中有大量的海洋细菌。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成功管理海洋种群和生产性水产养殖。海胆的免疫系统缺乏人类存在的重要方面。例如，海胆不会产生抗体。相反，它们表达一种名为Transformer Proteins的抗病原体蛋白家族(它们会改变形状！)至少有一种Transformer蛋白的作用非常广泛，可以与细菌、真菌和其他病原体结合。这与只结合一个靶点的一种抗体有很大不同。假设每个转换器蛋白有一个略有不同的靶标，这给了海胆很大的灵活性，以保护自己免受具有相似、不同或重叠靶标的病原体的攻击。由于转换蛋白的种类繁多，略有不同，它们复杂的抗病原体活性可能是海胆生存所必需的。该项目以以下方式将研究与教育相结合。科学的艺术插图是向公众传播科学的有效手段。生物学和艺术系将专门为美术专业的学生设计和教授一门生物学入门课程。艺术家/科学家的合作可以提高人们是否学习和理解科学中的重要概念，这将有助于科学素养。此外，环境政策学生对科学理解的提高可能会对政府的官方政策产生影响。海胆具有复杂而强大的抗病原体天然免疫系统，部分由SpTransformer(SpTrf；以前的Sp185/333)蛋白组成。重组(R)SpTrf-E1蛋白能与弧菌和酵母结合，但不能与芽孢杆菌结合。它能结合内毒素、β-1，3-葡聚糖和鞭毛蛋白，但不能结合肽聚糖。RSpTrf-E1本质上是无序的，在阴离子靶标如PO4基团的存在下转变为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靶点。他们将尝试确定rSpTrf-E1的结合部位，确定与其他rSpTrf蛋白结合的靶点，确定其他rSpTrf蛋白是否像(R)SpTrf-E1一样经历构象转化，并测试其他SpTrf蛋白在体外和体内的抗病原体活性。研究结果有望阐明SpTrf蛋白的结合和结构特征及其在宿主防御中的活性，为基础后口的免疫适应提供了一个独特的例子。艺术说明科学是向公众传播科学的有效方式。然而，文科学生一般不会在标准的科学入门课程中学到很多东西。因此，生物学和艺术系将专门为美术专业的学生设计和教授一门生物学入门课程。艺术的灵感将来自于从讲座、讨论和与科学家的接触中学到的科学。结果将突出艺术家/科学家合作的机会，如改进的数据说明，以及环境科学政策学生学习可能对官方政府政策产生影响的科学中的重要概念。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.