Liu Andrew C, Lewis Warren G, Kay Steve A
Department of Biochemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. [
Nat Chem Biol. 2007 Oct;3(10):630-9. doi: 10.1038/nchembio.2007.37.
Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coordinates rhythmic physiology and behavior. Synchronization in the SCN and at the organismal level is a key feature of the circadian clock system. In particular, intercellular coupling in the SCN synchronizes neuron oscillators and confers robustness against perturbations. Recent advances in our knowledge of and ability to manipulate circadian rhythms make available cell-based clock models, which lack strong coupling and are ideal for target discovery and chemical biology.
机体中几乎所有细胞都有基于负反馈机制的细胞内生物钟机制。哺乳动物的昼夜节律计时系统是一个分层的多振荡器网络，其中视交叉上核（SCN）作为中央起搏器。SCN与日常的明暗周期同步，并协调有节律的生理和行为。SCN以及机体水平的同步是昼夜节律系统的一个关键特征。特别是，SCN中的细胞间耦合使神经元振荡器同步，并赋予对干扰的鲁棒性。我们在昼夜节律知识和操纵能力方面的最新进展产生了基于细胞的时钟模型，这些模型缺乏强耦合，非常适合用于靶点发现和化学生物学。
