Biochemical and Biophysical Mechanisms of Hydroid Allorecognition

海绵、水母、珊瑚和海鞘等群居动物可以根据细胞接触区分它们自己的组织和其他物种的组织，导致它们要么融合要么排斥的反应。这种现象被称为同种异体识别，由编码高度可变的同种异体识别分子的基因系统控制。尽管这些无脊椎动物的同种识别系统对殖民地生物的生活史很重要，但人们对它们的生化和生物物理基础仍然知之甚少。这项计划的目的是阐明这些机制在爬行动物，水龙共生。在Hydractinia中，同种异体识别由两个高度可变的基因alr1和alr2控制。在这个项目中，研究人员将使用体外生化分析和转基因动物体内遗传学方法相结合的方法来确定ALR蛋白的细胞外和细胞内配体，并表征它们在细胞信号转导中的作用。这些结果将解释ALR蛋白本身是如何区分自我和非我的，以及它们是如何向同种识别效应系统发出信号的。产生的数据还将使人们能够与其他自我识别系统进行比较，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，如果在海鞘异种识别系统或脊椎动物免疫系统之间发现同源性，这将表明现有的自我识别系统是从所有后生动物的最后一个共同祖先中存在的系统进化而来的。该项目将包括为本科生、研究生和博士后提供培训机会，为地区高中生提供研究机会，以及向宾夕法尼亚州西南部的中小学生提供教育推广。这项工作的结果将被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为移植患者所做的演讲和时事通讯。

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.