Molecular Mechanisms of Seasonal Time Measurement

项目摘要/摘要 未能对季节变化做出反应会对生物体的生存能力和 繁殖。对于人类来说，周围环境的季节性波动，特别是光量， 会导致季节性情感障碍，以及心血管和免疫相关疾病。在动物身上 和植物，繁殖精确地与特定的季节保持一致。许多生物，包括人类，都有 进化的感知机制，通过调整动态平衡、生理学为即将到来的季节变化做好准备 和发展。我们研究计划的长期目标是通过以下方式阐明分子机制 哪些生物衡量季节变化、日长和温度的特殊性。尽管我们知道 外部刺激(光和温度)和内部生物钟之间的相互作用 在季节性反应中，涉及的分子调控网络在很大程度上仍然难以捉摸。季节性时间 几十年来，测量一直是时间生物学的重要主题之一，我们已经了解到 这些网络的相似类型或结构在动物和植物中都存在。在模式生物中 在这项研究中，我们对模式植物拟南芥的知识是最先进的。在拟南芥中， 环境光和温差通过分子时钟网络进行处理，以调节 转录一个成花基因，称为成花基因T(FT)。我们主要关注的是 阐明FT转录是如何被调控的。尽管昼夜节律依赖于时钟的季节性感觉 机制是FT表达的主要控制者，其他外部和内部信息被导入 调节FT转录以精确决定开花的时间。在本提案的目标1中，我们 将获得更精确的表观基因组和转录信息 不要在组织/细胞类型的水平上表达FT。有了这些信息，我们将能够组织我们目前的 了解FT在整个植物水平上的调控，以实现更精确的组织/细胞类型的特定调控。 通过对自然界生长的植物的研究，我们最近发现了一种受光控制的FT转录调控 而生物钟在这一点上还完全没有特征。我们将研究分子 目标2中这种调节的基础机制。我们在季节性感知机制方面的工作提供了 关于光感受器FKF1的功能知识。在目标3中，我们将获得更准确的关于 这种光感受器是如何通过调节光激发态的长度和分析生化变化来构建的 输出功能。这些信息将帮助我们了解这种光感受器的光化学特征 控制功能输出；它还可能为我们提供更多的光遗传工具。这些发现将会有一个 对植物研究和我们对季节感应和昼夜节律时钟的更广泛理解产生了重大影响 哺乳动物和其他系统，包括人类。

PROJECT SUMMARY/ABSTRACT Failure to respond to seasonal change has severe consequences for an organism’s ability to survive and reproduce. For humans, seasonal oscillation in the surrounding environment, especially the amount of light, can cause Seasonal Affective Disorder, as well as cardiovascular and immunity-related diseases. In animals and plants, reproduction is precisely aligned with specific seasons. Many organisms, including humans, have evolved sensing mechanisms to prepare for upcoming seasonal changes by adjusting homeostasis, physiology and development. The long-term goal of our research program is to elucidate the molecular mechanisms by which organisms measure seasonal changes, particularity in day length and temperature. Although we know that the interplay between external stimuli (light and temperature) and the internal circadian clock orchestrates seasonal responses, the molecular regulatory networks involved have remained largely elusive. Seasonal time measurement has been one of the important topics in chronobiology for decades, and we have learned that similar types or structures of these networks exist in both animals and plants. Among the model organisms used in this research, our knowledge of the model plant Arabidopsis is the most advanced. In Arabidopsis, ambient light and temperature differences are processed through the molecular clock network to regulate the transcription of a florigen (flower-inducing) gene called FLOWERING LOCUS T (FT). Our major focus is elucidating how FT transcription is regulated. Although the circadian clock-dependent seasonal sensing mechanism is the major controller of FT expression, other external and internal information is channeled into the regulation of FT transcription to precisely determine the timing of flowering. In Aim 1 of this proposal, we will obtain more precise epigenomic and transcriptomic information in both FT-expressing cells and cells that do not express FT at the tissue/cell-type levels. With this information, we will be able to organize our current understanding of FT regulation at the whole plant level into more precise tissue/cell-type specific regulation. Through our study of plants grown in nature, we recently found an FT transcription regulation controlled by light and the circadian clock that had been completely uncharacterized up to this point. We will study the molecular mechanisms underlying this regulation in Aim 2. Our work in seasonal sensing mechanisms has provided functional knowledge about the photoreceptor FKF1. In Aim 3, we will obtain more precise knowledge about how this photoreceptor is built by tuning the length of light-excited states and analyzing changes in biochemical output function. This information will help us understand how the photochemical features of this photoreceptor control functional outputs; it will also likely provide us with more optogenetic tools. The findings will have a large impact on plant research and our broader understanding of seasonal sensing and circadian clocks in mammals and other systems, including humans.