Function and Regulation of Metacaspases in Plant Cell Death

程序性细胞死亡(PCD)存在于所有真核生物中，在组织/器官形态发生、清除有害/受损细胞、病原体防御和应激反应等重要过程中发挥重要作用。Metacaspase属于一个特殊的半胱氨酸蛋白酶家族，在植物、真菌和原生动物中被发现是这一重要过程的高度保守的调节者，但它们的调控模式和下游靶标在大多数情况下仍然不清楚。该项目将开展遗传学和分子研究，旨在阐明控制偏半胱氨酸酶的激活和脱敏的机制。此外，研究人员将部署一种新的技术来定义三种不同的偏半胱氨酸酶的细胞内靶点，以揭示这些酶调控的潜在途径。除了对我们了解高等植物中PCD调控的直接贡献外，该项目还将阐明保守的偏半胱氨酸酶如何被调控的机制。这些进展有助于未来设计新的策略来激活致病原生动物品系和真菌中的细胞死亡，以及在胁迫期间抑制作物中的细胞死亡以提高生产力。该项目产生的结果将通过同行评议的期刊向公众公布，产生的资源，如新的突变系和DNA构建，将根据要求与其他研究人员自由分享。从教育学的角度来看，该项目将为博士后研究人员和研究生和本科生提供多样化的跨学科培训。它将使团队成员接触到一系列不同的学科，包括遗传学、基因组学、分子克隆、生物化学和细胞生物学。这种基础广泛的培训将提供一个丰富的环境，有利于采用创造性的方法解决生物学中的复杂问题，并利用创新技术提供新的解决方案。

Programmed cell death (PCD) is found in all eukaryotes and plays critical roles in important processes such as tissue/organ morphogenesis, elimination of unwanted/damaged cells, pathogen defense, and stress responses. Metacaspases belong to a family of specialized cysteine proteases that are found to be highly conserved regulators of this important process in plants, fungi and protozoa but their mode of regulation and downstream targets remain obscure in most cases. This project will carry out genetic and molecular studies aimed at elucidating the mechanisms by which the activation and desensitization of metacaspases may be controlled. Furthermore, the investigators will deploy a novel technology to define the intracellular targets for three different metacaspases in order to uncover the potential pathways that are regulated by these proteases. In addition to the direct contributions toward our understanding of PCD regulation in higher plants, this project will shed light on the mechanisms of how the conserved metacaspases could be regulated. These advances can facilitate future design of novel strategies to activate cell death in pathogenic protozoa strains and fungi, as well as to suppress cell death in crop plants during stresses for improved productivity. Results generated from this project will be communicated to the public via peer-reviewed journals, and the resources produced, such as new mutant lines and DNA constructs, will be freely shared with other investigators upon request. From the pedagogical perspective, this project will provide diversified, interdisciplinary training to postdoctoral researchers and students at both the graduate and undergraduate levels. It will expose team members to a diverse array of disciplines, including genetics, genomics, molecular cloning, biochemistry and cell biology. This broad-based training will provide a rich environment that is conducive to creative approaches for solving complex problems in biology and for leveraging innovative technologies for novel solutions.