"Understanding the role of autophagy in the control of RNA trafficking, triage and translation"

在压力下，细胞会重新调整它们的基因表达程序和代谢途径，以限制损伤并存活到压力消除。这些细胞应激反应是复杂的，人们对其知之甚少，但越来越多的证据表明，它们在限制感染的损害和监测可能导致癌症的异常细胞行为方面发挥着重要作用。这种细胞应激反应的一个例子是自噬，字面意思是“自我吞噬”。自噬是一种进化上保守的过程，它通过促进各种细胞结构的降解和再循环，从而为细胞的生存提供必要的细胞构件和能量，从而使细胞在饥饿的压力下存活下来。有趣的是，压力也被证明通过影响全球信使RNA （mRNA）的周转和翻译来影响基因表达。应激反应的一个核心特征是快速和可逆的翻译抑制，这可以防止异常蛋白的积累，促进关键应激反应蛋白的产生。翻译失活的mrna -蛋白复合物形成大的细胞质聚集体，称为应激颗粒（SGs）。SGs在控制应激期间的翻译机制中起着核心作用，作为翻译非活性转录本被分类并路由到重新启动或降解位点（例如加工体）的位点。尽管它们在控制基因表达和维持细胞稳态方面具有重要且可能互补的作用，但自噬和SGs/p-小体之间的关系迄今尚未被探索。目前的建议旨在阐明这些复杂的稳态机制之间的关系，使用一套分子工具和高分辨率成像技术。这项工作将为在压力时期控制基因表达的基本细胞过程提供新的见解。

In times of stress, cells re-prioritize their gene expression programs and metabolic pathways in order to limit damage and survive until the stress is resolved. These cellular stress responses are complex and poorly understood, but accumulating evidence indicates that they play important roles in limiting the damage of infection, and monitoring aberrant cellular behaviour that might lead to cancer. One example of such a cellular stress response is autophagy, which literally means 'self-eating'. Autophagy is an evolutionarily conserved process that permits cells to survive the stress of starvation by promoting the degradation and recycling of a variety of cellular structures, thereby providing essential cellular building blocks and energy for survival. Interestingly, stress has also been shown to impact gene expression by influencing global messenger RNA (mRNA) turnover and translation. A central feature of the stress response is rapid and reversible inhibition of translation, which prevents the accumulation of aberrant proteins and facilitates the production of key stress response proteins. Translationally inactive mRNA-protein complexes nucleate the formation of large cytoplasmic aggregates known as stress granules (SGs). SGs play a central role in controlling the translation machinery during stress, serving as sites where translationally-inactive transcripts are triaged and routed to sites of re-initiation or degradation (e.g. processing-bodies). Despite their important and perhaps complementary roles in controlling gene expression and maintaining cellular homeostasis, the relationship between autophagy and SGs/p-bodies has not been explored to date. The current proposal is aimed at elucidating the relationship between these complex homeostatic mechanisms, using a suite of molecular tools and high-resolution imaging techniques. This work will provide new insights into the fundamental cellular processes that control gene expression during times of stress.