Understanding roles of non-coding RNAs in apoptosis-induced proliferation

细胞凋亡是细胞程序性死亡的一种主要形式，在多细胞生物体中，细胞凋亡通常在应激反应中被激活，以清除受损细胞。因此，它是健康的守护者。然而，长期以来，组织在受损细胞被移除后如何恢复一直是一个谜。我们和其他人的工作已经揭示，令人惊讶的是，凋亡细胞可以积极促进其邻近细胞的代偿性增殖，以维持组织的稳态，这一过程称为凋亡诱导增殖（AiP）。最近在包括果蝇和哺乳动物在内的几种生物体中的研究表明，AiP在组织恢复和再生中起着关键作用，并且在病理条件下，不受控制的AiP可导致过度的组织过度生长。然而，AiP在细胞和分子水平上的调控还不太清楚。这个博士项目旨在确定和验证非编码RNA在调节AiP中的作用。以果蝇为模式生物，综合运用遗传上位性、分子生物学、蛋白质组学、免疫组化、先进显微镜和定量数据分析等方法，系统地鉴定和鉴定AiP的新调控因子。由于AiP是进化保守的，该项目将为我们理解用于维持组织稳态和促进组织修复的细胞策略和遗传途径做出重大贡献。

Apoptosis, a major form of programmed cell death, is frequently activated in response to stress to remove damaged cells in multi-cellular organisms. It is therefore the guardian of health. However, it has long been a mystery how tissue recovers after damaged cells are removed. Work by us and others has revealed that, surprisingly, apoptotic cells can actively promote compensatory proliferation of their neighbouring cells to maintain tissue homeostasis, a process termed Apoptosis-induced Proliferation (AiP). Recent studies in several organisms including Drosophila and mammals have revealed that AiP plays critical roles in tissue recovery and regeneration and, in pathological conditions, uncontrolled AiP can lead to excessive tissue overgrowth. Yet there is not much known about the regulation of AiP at the cellular and molecular level. This PhD project is designed to determine and characterise roles of non-coding RNAs in regulating AiP. By using Drosophila as a model organism, combined approaches including genetic epistasis, molecular biology, proteomics, immunohistochemistry, advanced microscopy and quantitative data analysis will be employed to systematically identify and characterise novel regulators of AiP. As AiP is evolutionary conserved, this project will make substantial contributions to our understanding of the cellular strategies and the genetic pathways used to maintain tissue homeostasis and promote tissue repair.