Genetic Analysis of Circadian Rhythms in Arabidopsis

描述(申请人提供)：这项提案的长期目标是了解生物钟如何在真核细胞中发挥作用。生物钟的目的是调节细胞过程，使它们在白天和晚上的特定时间发生。生物钟在所有的生命王国中都能找到，而功能正常的生物钟的存在被证明可以增强生物体的健康。我们最初的基因发现计划产生了一个关键的时钟基因TOC1，它是一个新的光感受器家族ZTL的创始成员，在包括拟南芥在内的许多模式生物中，我们采用了正向遗传方法来理解时钟功能。这个基因发现计划的成功验证了这种方法，尽管目前阿拉伯紫质的昼夜节律屏幕还没有饱和，因为我们仍然在识别新的时钟基因。我们将继续对现有突变体进行表征，并通过开发基于TOC1的新记者来分离新的突变体，TOC1是从我们之前的筛选中确定的关键成分。此外，我们将利用反向遗传方法来探索关于时钟基因家族成员在生物钟中所起作用的假设。鉴于昼夜节律调节生理学的普遍存在，识别常见的时钟成分将对理解起搏器的机制和与人类福祉的已知特征相关的故障产生影响。 公共卫生相关性：几乎所有生物体都有生物钟，控制生理、新陈代谢和行为的日常节奏。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学到的进展将广泛适用于理解人类的节律以及与其在广泛疾病中的功能障碍相关的已知病理。

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.