Defining the role of stress granules (SG) in RNA stability and translation.

在进化的早期，细胞已经发展出非常复杂的机制来检测、响应和适应压力环境。对各种压力的抵抗和适应，特别是通过修复机制和基因表达的重编程，是后生动物细胞行为的基本决定因素。细胞对应激的反应涉及信号转导机制，这些信号转导机制始于病变部位（即DNA、蛋白质、细胞骨架聚合物结构或细胞器），然后传播到核心细胞机制，以产生高度协调的细胞反应。因此，细胞应对各种压力的能力依赖于复杂的机制，这些机制在空间和时间上都是精细调节的，表现出高度的细胞间异质性，并且经常涉及瞬时和高度特化的亚细胞结构的组装。******申请人Mazroui， Huot， fraet - turcotte和Lavoie是拉瓦尔大学的早期，中期和高级女性/男性首席研究员，他们在阐明细胞对应激反应的各个方面做出了重大贡献，包括DNA损伤反应，应激诱导的RNA或蛋白质区化和翻译，细胞分裂和死亡，以及细胞粘附和运动性。所有四名申请者都开发了nserc资助的项目，这些项目严重依赖于对压力反应的动态亚细胞结构的成像。一个更灵敏、更快速的共聚焦系统将大大有利于申请人的研究项目，以获取高分辨率的大型成像数据集。本申请是为我们现有的蔡司LSM 700系统首次升级到高性能的LSM 900共聚焦系统请求资金。该设备将极大地加速与广泛相关的细胞生物学领域的知识，同时使用最先进的技术在HPQ培训中保持高质量标准。******我们的主要扫描共聚焦系统LSM 700是10年前获得的，不适合检测弱的接近生理的蛋白质或量化亚细胞结构动力学，因为它缺乏灵敏度和扫描速度。我们建议更换共聚焦头，探测器以及激光模块，以受益于新一代LSM 900的主要优点。我们迫切需要一套为活细胞成像而优化设计的敏感共聚焦系统，这不仅是为了保持我们团队的竞争力，也是为了用最先进的技术维持高质量的HPQ培训标准。* * * * * * * *

Early during evolution, cells have developed very sophisticated mechanisms to detect, respond and adapt to stressful environment. Resistance and adaptation to various stresses, notably through repair mechanisms and reprogramming of gene expression, are fundamental determining factors in the behavior of metazoan cells. The cellular responses to stress involve signal transduction mechanisms that are initiated at the lesion sites (i.e. DNA, protein, cytoskeletal polymeric structures or organelles) and then propagated to the core cellular machineries to generate a highly coordinate cellular response. Therefore, the ability of cells to cope with various stresses relies on complex mechanisms that are finely tuned spatially and temporally, exhibit high intercellular heterogeneity, and often involve the assembly of transient and highly specialized subcellular structures. ******The applicants Mazroui, Huot, Fradet-Turcotte and Lavoie are early, mid-career, and senior female/male principal investigators at Université Laval, who made significant contributions in elucidating various aspects of the cellular responses to stress, including DNA damage response, stress-induced RNA or protein compartmentalization and translation, cell division and death, and cell adhesion and motility. All four applicants have developed NSERC-funded programs that heavily rely on imaging of dynamics subcellular structures in response to stress. The research programs of the applicants would significantly benefit from a more sensitive and rapid confocal system for the acquisition of large imaging datasets at high resolution. This application is to request funding for a first upgrade of our existing Zeiss LSM 700 system to a high performance LSM 900 confocal system. This equipment would tremendously accelerate knowledge on Cell Biology areas with widespread relevance, while maintaining high quality standards in HPQ training using state-of-the art technologies. ******Our main scanning confocal system, the LSM 700, was acquired 10 years ago and is not suitable to detect weak near-to physiological proteins or to quantify subcellular structure dynamics, as it suffers from a lack of sensitivity and scanning speed. We propose to replace the confocal head, the detectors as well as the laser module to benefit from major advantages of the new generation LSM 900. The acquisition of a sensitive confocal system optimally designed for live-cell imaging is urgent, not only for our groups to maintain their competitiveness, but also to sustain the high-quality training standards for HPQ with state-of-the-art technologies.****** **