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 Pyroptosis是一种程序化的火灾试验。 项目摘要 炎性细胞死亡程序pyroptosis发生在广泛的细胞类型和发挥重要作用 在发育、组织损伤和肿瘤生长中的作用。奇怪的是，与其他细胞死亡机制不同， 存活于焦亡激活。一个“低效”细胞死亡基因家族的持续存在令人困惑， 他们可能有其他的角色。直觉上，在炎症损伤中存活下来的细胞将决定短期的 适应和长期的修复和再生。因此，一个有缺陷的死亡程序 成为“审判”。然而，细胞凋亡后细胞存活的细节和其激活以外的生化回路， 都没有被充分研究，阻碍了我们的基本理解。在这个项目中，我们假设细胞死亡是一个侧面- 细胞凋亡的作用，其实际上旨在重新编程细胞功能。探索“试错”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pyroptosis 以及用于施加这种控制的基本机制; 2）焦亡信号传导的能力和限制;以及3） 风化焦亡的单细胞表型效应。在追求这一核心假设的过程中，我们将发现 新的细胞信号电路，同时提高该领域的能力，以检测新的途径， 新的遗传编码工具、成像算法和生物信息学方法。该计划旨在建设 一个新的观点认为，焦亡的突出功能是通过濒死体验来激发和教育。 拟议的行政补充将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， 可以产生细胞凋亡信号。