Biochemical and Biophysical Mechanisms of Hydroid Allorecognition

海绵、水螅、珊瑚和海鞘等群居动物可以根据细胞接触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。这种现象被称为同种异体识别，是由编码高度可变的同种异体识别分子的遗传系统控制的。尽管它们对殖民地生物的生活史很重要，但这些无脊椎动物异体识别系统的生化和生物物理基础仍然知之甚少。本课题的目的是阐明这些机制在刺胞动物，水螅共生。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，研究人员将结合体外生化分析和体内遗传方法，与转基因动物一起鉴定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，以及它们如何向异体识别效应系统发出信号。生成的数据还可以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。在动物中，如果发现水螅异体识别系统与海鞘异体识别系统或脊椎动物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最后共同祖先的系统进化而来的。该项目将为本科生、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，并为宾夕法尼亚州西南部的中学生和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报告和通讯。

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.