Genetic Analysis of Circadian Rhythms in Arabidopsis

描述（由申请人提供）：本提案的长期目标是了解生物钟如何在真核细胞内发挥作用。生物钟的目的是调节细胞过程，使它们在白天和黑夜的特定时间发生。生物钟存在于生命的所有王国中，并且功能性生物钟的存在已被证明可以增强生物体的适应性。了解时钟功能的正向遗传学方法在许多模式生物（包括拟南芥）中发挥了重要作用，我们最初的基因发现计划产生了一个关键的时钟基因TOC1和一个新的感光细胞家族ZTL的创始成员。这个基因发现计划的成功验证了这种方法，尽管目前Arabdopsis的昼夜节律筛选还没有饱和，因为我们仍在鉴定新的时钟基因。我们将继续对现有突变体进行表征，并通过开发基于TOC1的新报告基因来分离新的突变体，TOC1是我们之前筛选中确定的关键成分。此外，我们将利用反向遗传学的方法来探索时钟基因家族成员在生物钟中的作用的假说。鉴于昼夜节律调节生理学的普遍性，识别常见的时钟组件将对理解与人类健康的已知特征相关的起搏器机制和故障产生影响。 公共卫生相关性：几乎所有的生物体都具有控制生理、代谢和行为日常节律的生物钟。这些生物钟的分子结构在所有生物体中似乎都是相似的。因此，在拟南芥等模型系统中获得的进展将广泛适用于理解人类的节律以及与各种疾病中的功能障碍相关的已知病理学。

DESCRIPTION (provided by applicant): The long-term goal of this proposal is to understand how circadian clocks function within eukaryotic cells. The purpose of a circadian clock is to regulate cellular processes such that they occur at specific times of the day and night. Circadian clocks are found in all kingdoms of life and the presence of a functional circadian clock has been shown to confer enhanced fitness onto the organism. Forward genetic approaches to understanding clock function have been instrumental in numerous model organisms including Arabidopsis and our initial gene discovery program yielded a key clock gene, TOC1, and the founding member of a novel photoreceptor family, ZTL. The success of this gene discovery program validates the approach, although currently circadian screens in Arabdopsis are not saturated since we are still identifying novel clock genes. We will continue the characterization of existing mutants and isolate novel mutants by developing new reporters based on TOC1, a critical component identified from our previous screens. In addition, we will exploit reverse genetic approaches to explore hypotheses about the role of clock gene family members in the circadian clock. Given the ubiquity of circadian-regulated physiology, the identification of common clock components will have an impact on understanding the pacemaker mechanism and malfunctions associated with known features of human well-being. PUBLIC HEALTH RELEVANCE: Almost all organisms possess circadian clocks that control daily rhythms in physiology, metabolism and behavior. The molecular architecture of these clocks appears similar amongst all organisms. Thus the advances learned in model systems such as Arabidopsis will be broadly applicable to understanding rhythms in humans and the known pathologies associated with their dysfunction in a wide range of diseases.