Cellular Mechanisms of Circadian Rhythm Generation

9601382罗伯茨神经系统最有趣的特征之一是它能够经历功能变化。这些变化可能是由于经验-学习-或者可能是基于神经细胞生理和生化的内部产生的变化。神经细胞功能的一个常见变化，几乎在包括人类在内的所有生物体中都观察到了，那就是伴随着日常环境中光明和黑暗的循环而发生的变化。有趣的是，神经细胞功能的这些日常变化并不是对环境的反射性反应，而是由内部计时系统调节的。内部计时系统由位于大脑或其他神经结构中的昼夜节律起搏器(大约一天死亡)或“生物钟”控制。过去几年对昼夜节律起搏器的研究表明，昼夜节律时钟和昼夜节律系统的功能中断会导致人类生理上的多种问题。此外，昼夜节律系统(内部节律性)之间的相互作用对于充分了解生物体与其环境的关系至关重要。最后，已经证明生物时钟通过许多细胞内生化过程的相互作用来发挥作用，如基因转录、翻译和蛋白质修饰。我们工作的目的是在一个模型神经系统中研究生物钟功能的生物化学。在这些研究中，我们将分析两类特定的蛋白质(周期蛋白依赖蛋白激酶和丝裂原激活蛋白激酶)在海洋蜗牛眼睛产生的昼夜节律的产生和调节中所起的重要作用。对几种不同的昼夜节律起搏器的研究表明，时钟功能在不同的生物体群体中是保守的。因此，我们的研究应该提供关于昼夜节律产生的生物化学的一般性见解。

9601382 Roberts One of the most interesting features of the nervous system is the fact that it is able to undergo functional changes. These changes may occur due to experience - learning - or may be based upon internally generated changes in nerve cell physiology and biochemistry. One common change in nerve cell function, that has been observed in virtually all organisms including humans, are the changes that follow the daily environmental cycle of light and darkness. Interestingly, these daily changes in nerve cell function are not reflexive responses to the environment, but instead are regulated by an internal timing system. The internal timing system is controlled by circadian pacemakers (circa - about dies - a day) or "biological clocks" located in the brain or other neural structures. Investigation of circadian pacemakers over the past several years has indicated that disruption in the function of the circadian clock, and the circadian timing system, leads to multiple problems in human physiology. Furthermore, the interaction between the circadian timing system (internal rhythmicity) is of critical importance in gaining a full understanding of an organism's relationship with its environment. Finally, it has been shown that biological clocks function through the interaction of many intracellular biochemical processes such as gene transcription, translation, and protein modification. The purpose of our work is to investigate the biochemistry of circadian clock function in a model neural system. In these studies we will analyze the role played by two specific classes of protein (cyclin-dependent kinases, and mitogen activated protein kinases) that we propose are important in the generation and regulation of the circadian rhythm produced in the eye of the marine snail, Bulla gouldiana. Investigation of several different circadian pacemakers has shown that clock function has been conserved in a diverse group of organisms. Thus, our studies should pr ovide general insights concerning the biochemistry of circadian rhythm generation.