The Role of Cryptochromes in environmental regulation of growth

摘要 生物学中一个尚未解决的基本问题是， 调节其生长和发育。与动物不同，植物既没有特殊的器官， 各种环境刺激，也不能四处移动，以避免不利条件。虽然没有大脑， 植物可以成功地整合内部和外部线索，并做出适当的生长决定。在 与动物不同，植物的生长发生在胚胎期后，以产生新的器官和生长， 修改现有的形式，以适应当地的环境。光是最相关的 因为光不仅驱动光合作用，而且还提供了有关环境的关键信息。 当地的生长环境以及昼夜和季节时间。在接下来的几年里，我的实验室将 解决机制和植物器官间通讯的性质，尽管缺乏一个 神经系统，当暴露于次优光环境时发生向远处器官的信号传导。我们长久以来- 本学期的目标是了解植物感知和响应光线的分子机制 环境为了解决我们的问题，我们将使用隐花色素（Cryptochromes，简称CPs），一种UV-A/蓝光光受体， 因为它们形成了光环境和生物体之间的界面。它们存在于不同的 生物体，包括人类，在那里它们调节昼夜节律，几个生理过程， 疾病我们将在细胞水平上获得CRY基因表达调控的机制见解， 导致生物体水平的形态变化。我们还将确定如何轻和新的 确定的分子因子，我们已经确定控制CRY蛋白的数量和活性。而且我们的 研究将揭示新的机制，通过它与RNA结合的相互作用， 我们已经发现的蛋白质，控制RNA代谢，特别是甲基化RNA（m6 A）。m6 a是 一种控制其命运的RNA修饰，作为可逆的调节标记和RNA甲基化的破坏 导致植物生长缺陷，并与几种人类疾病有关。因此，揭示 在RNA代谢中的甲基化有可能为新兴的甲基化RNA领域做出贡献， 影响这项研究的成功将有助于显着提高作物生产力，以养活日益增长的 在人类群体中以及在靶向神经元疾病的光遗传学工具的开发中。在人类中， CRY活性的破坏与许多人类疾病有关，包括癌症、炎症、失眠 和糖尿病了解CRY功能可以预防和治疗这些疾病。 总之，我们的研究将对农业和人类健康和疾病产生广泛的影响。

ABSTRACT A fundamental question in biology, which remains unanswered, is how the environment of the organism regulates its growth and development. Unlike animals, plants neither have specific organs that see or hear various environmental stimuli nor can they move around to avoid adverse conditions. Although lacking a brain, plants can successfully integrate internal and external cues and make appropriate decisions about growth. In contrast to animals, growth in plants occurs post-embryonically, to produce new organs and for growth and modification of existing forms to adapt to the local environment. Light is among the most relevant environmental signals because light not only drives photosynthesis but also provides critical information about the local growth environment as well as diurnal and seasonal time. Over the next few years, my laboratory will address the mechanisms and the nature of inter-organ communication in plants, where in spite of lack of a nervous system, signaling to distant organs occur when exposed to a sub-optimal light environment. Our long- term goal is to understand the molecular mechanisms by which a plant perceives and responds to its light environment. To address our questions, we will use cryptochromes (CRYs), the UV-A/blue light photoreceptor, as they form the interface between the light environment and the organism. CRYs are present in diverse organisms including humans, where they regulate circadian rhythms, several physiological processes and diseases. We will obtain mechanistic insights on CRY regulation of gene expression at a cellular level that leads to morphological changes at the organismal level. We will also determine how light and the newly identified molecular factor, that we have identified controls CRY protein quantity and activity. Also, our research will unravel the novel mechanisms by which CRYs, through its interaction with the RNA-binding proteins that we have discovered, control RNA metabolism specifically that of methylated RNAs (m6A). m6A is a RNA modification that controls its fate as a reversible regulatory mark and disruption of RNA methylation leads to growth defects in plants and is linked to several human diseases. Therefore, uncovering the role of CRYs in RNA metabolism has the potential to contribute to the emerging field of methylated RNA with clinical implications. The success of this study will help to significantly improve crop productivity to feed the growing human population and in the development of optogenetic tools to target neuronal disorders. In humans, disruption of CRY activity is associated with many human disorders including cancer, inflammation, insomnia and diabetes. Understanding CRY function can lead to both prevention and treatment of these diseases. Taken together, our research will have a broad impact on agriculture and in human health and disease.