The Need for Speed: Understanding the Importance of Different ELF3 Nuclear Localisation Mechanisms

生物钟是一种内源性的计时机制，使生物体能够协调其内部的生理反应与外部环境。植物生物钟的操控对植物驯化至关重要，而时钟功能的进一步改变将有助于培育出适应气候变化的作物品种。在过去三十年的植物昼夜节律研究中，我们开发了详细的时钟系统的遗传和数学模型。相比之下，研究植物生物钟的蛋白质动力学的研究才刚刚起步。昼夜节律蛋白在细胞中何时何地活跃在很大程度上仍不清楚。从蛋白质的角度了解生物钟对于完全概念化和理解基因突变对功能和表型的影响是必要的。这项研究将研究植物生物钟早期开花蛋白3(ELF3)的细胞动力学，ELF3是植物生物钟中的关键枢纽蛋白。到目前为止，ELF3的所有功能都依赖于它对细胞核的定位。然而，目前还不清楚ELF3是如何到达细胞核的。最初，ELF3被认为通过一个特定的序列基序定位于核。然而，这个序列基序只存在于少数植物物种中。相反，我的研究表明ELF3通过与其他蛋白质的相互作用定位于细胞核。了解这些蛋白质-蛋白质相互作用如何介导ELF3的核定位对于了解ELF3的功能至关重要。拟议的工作将利用细胞、生化和遗传学方法，为ELF3如何定位到细胞核以及这一机制对其整体功能的贡献提供新的基本见解。

Circadian clocks are endogenous timekeeping mechanisms that enable organisms to coordinate their internal physiological responses with the external environmental. Manipulation of the plant circadian clock has been critical for plant domestication, while further alterations to clock function will contribute to the generation of crop varieties suitable for the changing climate. Over the last three decades of plant circadian research, we have developed detailed genetic and mathematical models of the clock system. In contrast, studies investigating the protein dynamics of the plant circadian clock are nascent. Where and when circadian proteins are active in the cell remains largely unknown. Understanding the circadian clock from a protein perspective is necessary to fully conceptualise and understand the impact of gene mutations on function and phenotype.The research proposed in this fellowship will investigate the cellular dynamics of the plant circadian protein EARLY FLOWERING3 (ELF3), a key hub protein within the plant circadian clock. So far, all functions of ELF3 are dependent on its localisation to the nucleus. However, it remains unknown how ELF3 arrives in the nucleus. Originally, ELF3 was proposed to localise to the nucleus through a specific sequence motif. However, this sequence motif is present in only a small number of plant species. Instead, my research suggests that ELF3 localises to the nucleus through interactions with other proteins. Understanding how these protein-protein interactions mediates the nuclear localisation of ELF3 is critical in understanding how ELF3 functions.The proposed work will utilise cellular, biochemical, and genetic approaches to provide new fundamental insights into how ELF3 localises to the nucleus and the contribution of this mechanism for its overall functionality.