Pyroptosis is a Trial-by-Fire Program

细胞焦亡是一个试炼程序

• 批准号: 10796433
• 负责人: Gary CH Mo
• 金额: $ 24.92万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10796433
• 关键词: Administrative Supplement; Algorithms; Biochemical; Bioinformatics; Cell Death; Cell Separation; Cell Survival; Cell physiology; Cells; Cessation of life; Curiosities; Data; Development; Evolution; Family; Fire - disasters; Fluorescence; Gene Family; Genes; Image; Inflammatory; Intuition; Methods; Natural regeneration; Near-Death Experience; Organism; Pathway interactions; Phenotype; Play; Protein Engineering; Role; Signal Transduction; Speed; Weather; cell killing; cell type; improved; novel; programs; repaired; side effect; sound; tissue injury; tool; tumor growth

TITLE Pyroptosis is a Programmed Trial-by-Fire. PROJECT ABSTRACT The inflammatory cell death program pyroptosis occurs in a wide range of cell types and plays important roles in development, tissue injury, and tumor growth. Curiously, unlike other cell death mechanisms, cells frequently survive pyroptosis activation. The persistence of a family of “inefficient” cell death genes is puzzling and suggests they may have other roles. Intuitively, cells that survive the inflammatory insult will dictate both the short-term adaptation and long-term repair and regeneration afterwards. Therefore, a flawed death program may actually be a “trial”. However, the details of cell survival after pyroptosis and the biochemical circuitry beyond its activation are under-studied, hindering our basic understanding. In this Program, we hypothesize that cell death is a side- effect of pyroptosis, which in fact aims to reprogram cell functions. To explore the new concept that “trial-by-fire” provides strong evolutionary advantages, we will investigate 1) whether it is possible to stop/resume pyroptosis and the basic mechanisms used to exert such control; 2) the capacity and limits of pyroptosis signaling; and 3) the single cell phenotypic effects of weathering pyroptosis. In pursuing this central hypothesis, we will discover new cell signaling circuits and simultaneously enhance the field’s ability to detect novel pathways by developing new genetically encoded tools, imaging algorithms, and bioinformatics methods. The Program aims to construct a new perspective that the salient function of pyroptosis is to prime and educate through a near-death experience. The proposed administrative supplement combines sound platforms like Fluorescence Assisted Cell Sorting with new technical developments in protein engineering to boost the scale and speed at which accurate data on pyroptosis signaling can be generated.

标题 上睑下垂是一种程序化的试火法。 项目摘要 炎性细胞死亡程序上睑下垂发生在多种细胞类型中，并发挥重要作用 在发育、组织损伤和肿瘤生长过程中。奇怪的是，与其他细胞死亡机制不同，细胞经常 在上睑下垂激活状态下存活。一个“低效”细胞死亡基因家族的持续存在令人费解，并表明 他们可能扮演着其他角色。直觉上，在炎性侮辱中幸存下来的细胞将决定短期内 适应和之后的长期修复和再生。因此，一个有缺陷的死亡程序实际上可能 成为一场“审判”。然而，上睑下垂后细胞存活的细节和超越其激活的生化回路 研究不足，阻碍了我们的基本理解。在这个节目中，我们假设细胞死亡是一个侧面- 上睑下垂的影响，这实际上是为了重新编程细胞功能。探索“火力审判”的新理念 提供强大的进化优势，我们将调查1)是否有可能停止/恢复下垂 用于实施这种控制的基本机制；2)上睑下垂信号的能力和限度；3) 风化性下垂的单细胞表型效应。在追寻这一中心假说的过程中，我们将发现 新的细胞信号电路，同时通过开发新的通路来增强该领域检测新途径的能力 新的基因编码工具、成像算法和生物信息学方法。该计划旨在构建 一种新的观点认为，上睑下垂的显著功能是通过濒死体验进行准备和教育。 拟议的行政补充将荧光辅助细胞分类等健全的平台结合在一起 随着蛋白质工程的新技术发展，以提高准确数据的规模和速度 可以产生下睑下垂信号。