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 焦亡是一种程序化的火刑考验。 项目摘要 炎症细胞死亡程序焦亡发生在多种细胞类型中并发挥重要作用 奇怪的是，与其他细胞死亡机制不同，细胞经常发生这种情况。 一系列“低效”细胞死亡基因的持续存在令人费解，并表明这一点。 直观上讲，在炎症损伤中幸存下来的细胞将决定短期的情况。 因此，一个有缺陷的死亡程序实际上可能是适应和长期的修复和再生。 然而，焦亡后细胞存活的细节以及其激活之外的生化回路。 的研究不足，阻碍了我们的基本理解。在这个项目中，我们努力认为细胞死亡是一个侧面。 细胞焦亡效应，其目的实际上是重新编程细胞功能，探索“火力试验”的新概念。 提供了强大的进化优势，我们将研究1）是否有可能停止/恢复焦亡 以及用于施加这种控制的基本机制；2) 细胞焦亡信号传导的能力和限制；以及 3) 在研究这一中心假设的过程中，我们将发现风化焦亡的单细胞表型效应。 新的细胞信号通路，同时通过开发增强该领域检测新途径的能力 该计划旨在构建新的基因编码工具、成像算法和生物信息学方法。 一种新的观点认为焦亡的显着功能是通过濒死体验来启动和教育。 拟议的行政补充结合了荧光辅助细胞分选等健全的平台 随着蛋白质工程的新技术发展，提高了准确数据的规模和速度 可以产生细胞焦亡信号。