Unexpected Immune Diversity in the Purple Sea Urchin

紫海胆中意想不到的免疫多样性

• 批准号: 0424235
• 负责人: L Courtney Smith
• 金额: $ 55万
• 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: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0424235&HistoricalAwards=false
• 关键词: Unexpected; Immune; Diversity; Purple; Sea

Unexpected Immune Diversity in the Purple Sea UrchinIn humans, the immune system has two subsystems: the innate and the adaptive immune systems. The innate system first recognizes the presence of a pathogen and alerts the adaptive system to make antibodies and directs other adaptive responses. However, only vertebrates have an adaptive system, while invertebrates such as the purple sea urchin survive with only the innate system. The sea urchin innate immune system responds to the presence of pathogens by marking them as foreign, which results in the uptake of the pathogens by cells capable of killing them. Recent study designed to identify genes that were turned on in response to the presence of bacteria showed that one particular gene, called 185/333, was activated significantly more than all the rest. Although the protein encoded by this gene has not been previously identified in other organisms and its function is unknown, analysis has shown a significant level of diversity in these proteins, reminiscent of the antibody diversity generated by the adaptive immune system in higher vertebrates. This variability includes the protein structure, which shows the presence and absence of 24 different regions and variability in the sequence of the amino acids. The protein appears to be secreted, has separate regions rich in glycine and histidine, repeated sequence regions that may be used to bind to cell surfaces, and short regions that are very acidic. Curiously, no clear mechanism to keep the protein stably folded was found. The diversity in the proteins was expected to be encoded by many genes in an animal like sea urchin, however, evidence suggests that there are only a few. In order to understand the diversity in the genes and how it may affect the functions of the encoded proteins, two major aims will be undertaken: Aim 1. Characterization of the gene(s). The number and structure of genes will be analyzed in order to reveal how different regions of the protein are linked together, uncover the source of the amino acid variability, and investigate the response to bacterial challenge by specific cell types. Aim 2. Characterization of protein(s). It will be determined when the proteins are produced with respect to bacterial challenge. The function(s) of the proteins will also be characterized and any functional diversity among the proteins will be identified. This project is an initial investigation of an unexpectedly diverse innate immune response mounted by the sea urchin towards bacterial pathogens and may lead to a significant change in the understanding of the immune responses in animals other than higher vertebrates. Broader impacts: A change in the understanding of invertebrate immune capabilities may eventually alter the approaches employed within the research community for investigating immune responses in animals other than vertebrates. Research training will be undertaken for graduate and post-doctoral students and will promote exchanges of both student and senior researchers between the US and the co-investigator's lab in Australia. Research opportunities for undergraduates will be available in our laboratories, and assistance will be offered to undergraduates searching for research opportunities for placement in other local laboratories. In the past, trainees were 69% women and 46% underrepresented minorities. This demographic is not expected to change in the future.

紫海胆中出乎意料的免疫多样性在人类中，免疫系统有两个子系统：先天免疫系统和适应性免疫系统。 先天系统首先识别病原体的存在，并提醒适应性系统产生抗体并指导其他适应性反应。然而，只有脊椎动物有一个适应系统，而无脊椎动物，如紫海胆生存只有先天系统。海胆先天免疫系统通过将病原体标记为外来物来对病原体的存在做出反应，这导致能够杀死病原体的细胞吸收病原体。最近的一项研究旨在识别对细菌存在做出反应的基因，结果显示，一个名为185/333的特定基因比其他所有基因都被激活。虽然由该基因编码的蛋白质先前未在其他生物中鉴定，并且其功能未知，但分析显示这些蛋白质具有显著的多样性水平，这让人想起高等脊椎动物中适应性免疫系统产生的抗体多样性。这种变异性包括蛋白质结构，其显示24个不同区域的存在和不存在以及氨基酸序列的变异性。该蛋白质似乎是分泌的，具有富含甘氨酸和组氨酸的单独区域，可用于结合细胞表面的重复序列区域，以及非常酸性的短区域。奇怪的是，没有发现保持蛋白质稳定折叠的明确机制。蛋白质的多样性被认为是由海胆等动物的许多基因编码的，然而，有证据表明只有少数几个。为了了解基因的多样性以及它如何影响编码蛋白质的功能，将采取两个主要目标：目标1。基因的表征。 将分析基因的数量和结构，以揭示蛋白质的不同区域如何连接在一起，揭示氨基酸变异性的来源，并研究特定细胞类型对细菌挑战的反应。目标2.蛋白质的表征。 将确定蛋白质产生的时间与细菌挑战有关。还将表征蛋白质的功能，并鉴定蛋白质之间的任何功能多样性。该项目是对海胆对细菌病原体的意外多样的先天免疫反应的初步调查，可能会导致对高等脊椎动物以外的动物免疫反应的理解发生重大变化。更广泛的影响：对无脊椎动物免疫能力的理解的改变可能最终改变研究界用于研究脊椎动物以外动物免疫反应的方法。将对研究生和博士后学生进行研究培训，并将促进美国和澳大利亚共同研究者实验室之间的学生和高级研究人员的交流。 本科生的研究机会将提供在我们的实验室，并提供援助，以本科生寻找研究机会安排在其他本地实验室。 过去，受训人员中69%是妇女，46%是代表性不足的少数民族。 预计这一人口结构在未来不会发生变化。