Biochemical and Biophysical Mechanisms of Hydroid Allorecognition

水螅同种异体识别的生化和生物物理机制

• 批准号: 1255975
• 负责人: Matthew Nicotra
• 金额: $ 44.5万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1255975&HistoricalAwards=false
• 关键词: Biochemical; Biophysical; Mechanisms; Hydroid; Allorecognition

Colonial animals such as sponges, hydroids, corals, and ascidians can discriminate between their own tissues and those of other members of their species based on cellular contact, leading to a response in which they either fuse or reject. This phenomenon, called allorecognition, is controlled by genetic systems encoding highly variable allorecognition molecules. Despite their importance to the life histories of colonial organisms, the biochemical and biophysical basis of these invertebrate allorecognition systems remains poorly understood. The goal of this project is to elucidate these mechanisms in the cnidarian, Hydractinia symbiolongicarpus. In Hydractinia, allorecognition is controlled by two highly variable genes, alr1 and alr2. In this project the investigators will use a combination of in vitro biochemical assays and in vivo genetic approaches with transgenic animals to identify extracellular and intracellular ligands for the alr proteins and to characterize their role in cell signaling. These results will explain how the alr proteins, by themselves discriminate self from non-self, and how they signal allorecognition effector systems. Data generated will also enable comparisons to other self-recognition systems, including plant self-incompatibility loci and fungal mating type loci. Within animals, if homology is discovered between the Hydractinia allorecognition system and the ascidian allorecognition system or the vertebrate immune system, it would suggest that extant self-recognition systems evolved from a system present in the last common ancestor of all metazoans. This project will include training opportunities for undergraduate, graduate, and post-doctoral students, research opportunities for area high school students, and educational outreach to middle and elementary school students in southwestern Pennsylvania. Results of this work will be incorporated into undergraduate and graduate immunology courses at the University of Pittsburgh, as well as presentations and a newsletter for transplant patients at the University of Pittsburgh Medical Center.

群体动物，如海绵、水螅、珊瑚和海鞘，可以根据细胞接触来区分自己的组织和其他物种的组织，从而产生融合或排斥的反应。 这种现象被称为异源识别，是由编码高度可变的异源识别分子的遗传系统控制的。 尽管它们的重要性，殖民生物的生活史，这些无脊椎动物的同种异体识别系统的生物化学和生物物理基础仍然知之甚少。 这个项目的目标是阐明这些机制的刺胞动物，Hydractinia symbiolongarpus。 在Hydractinia中，同种识别由两个高度可变的基因alr1和alr2控制。 在这个项目中，研究者将使用体外生化分析和体内遗传学方法相结合的转基因动物来鉴定alr蛋白的细胞外和细胞内配体，并表征它们在细胞信号传导中的作用。 这些结果将解释alr蛋白如何通过自身区分自我和非自我，以及它们如何向同种识别效应系统发出信号。 所产生的数据也将使比较其他自我识别系统，包括植物自交不亲和基因座和真菌交配型基因座。 在动物体内，如果海葵属的同种异体识别系统与海鞘属的同种异体识别系统或脊椎动物的免疫系统之间存在同源性，则表明现存的自我识别系统是从所有后生动物的最后共同祖先中存在的系统进化而来的。该项目将包括本科生，研究生和博士后学生的培训机会，地区高中学生的研究机会，以及宾夕法尼亚州西南部中小学生的教育推广。 这项工作的结果将纳入匹兹堡大学的本科生和研究生免疫学课程，以及匹兹堡大学医学中心的移植患者简报和时事通讯。