Protein degradation mechanisms that regulate daily and seasonal timing

项目摘要/摘要 生物钟是使生物过程与环境的日常变化同步所必需的，但 生物体也需要测量光周期(日长)，并使生理与季节保持一致。 在理解驱动日常和季节性的转录联系方面取得了迅速的进展 时机到了。我们对翻译后机制，如蛋白质降解如何调节 生物钟和季节计时。植物，如拟南芥，一直是 了解生物钟，特别是生物钟如何调节光周期测量。 在上一次米拉奖的资助期间，我的实验室一直致力于蛋白质界面的研究 降解和生物钟，发现调节昼夜节律的蛋白质降解机制 时钟和季节生理学。在资助期间，我们还发现E3泛素连接酶之一 在我们的研究中是由植物中的非标准光周期测量系统控制的，打开了一个新的，但 相辅相成，我们实验室的研究途径。我们未来的工作将建立在这些基础研究的基础上 解决两个主要目标1)对控制三个E3泛素连接酶家族的 重要的时钟输出过程和2)继续识别和研究非典型光周期 植物中的测量系统。 这些研究将揭示生物钟如何控制日常和季节性生物学的一般原理。 生物钟调节着许多生物体的基本生物过程，而生物钟功能失调。 增加人类疾病和情绪障碍的患病率。因此，我们所做的工作将远远- 达到影响并符合NIGMS的目标，因为：1)它将提供基本原理和分子逻辑 真核生物生物钟系统，2)它将提供一个更全面的理解后- 覆盖时钟转录反馈环的翻译机制，以及3)它将作为一个框架 在包括人类在内的其他真核生物计时系统中进行类似的研究。

Project Summary/Abstract The circadian clock is necessary to synchronize biological processes with daily changes in the environment, but it is also required for organisms to measure photoperiod (daylength) and align physiology with the seasons. Rapid progress has been made in understanding the transcriptional connections that drive daily and seasonal timing. We know less about how post-translational mechanisms, such as protein degradation regulate the circadian clock and seasonal timing. Plants, such as Arabidopsis, have served as preeminent model systems for understanding the circadian clock, and in particular, how the circadian clock mediates photoperiod measurement. In the period of funding from the previous MIRA award, my laboratory has worked at the interface of protein degradation and the circadian clock, discovering protein degradation mechanisms that regulate the circadian clock and seasonal physiology. During the funding period, we also discovered that one of the E3 ubiquitin ligases in our study is controlled by a non-canonical photoperiod measurement system in plants, opening a new, but complementary, avenue of research in our lab. Our future work will build on these foundational studies by addressing two major goals 1) performing detailed investigations of three E3 ubiquitin ligase families that control important clock output processes and 2) continuing to identify and study non-canonical photoperiod measurement systems in plants. These studies will uncover general principles about how the circadian clock controls daily and seasonal biology. The circadian clock regulates fundamental biological processes in many organisms, and clock dysfunction increases the prevalence of human disease and mood disorders. Thus, the work that we perform will have far- reaching impacts and fits the goals of NIGMS because: 1) it will provide basic principles and molecular logic for eukaryotic circadian clock systems, 2) it will provide a more comprehensive understanding of the post- translational mechanisms that overlay transcriptional feedback loops of clocks, and 3) it will serve as a framework for similar studies in other eukaryotic timing systems, including humans.