Circadian Programming of Gene Expression in Cyanobacteria

所有生物复杂性水平的生物体都表现出由内源性生化振荡器控制的昼夜节律。这些生物钟的生化性质一直是难以捉摸的，但一个已经出现的原理是，它们的显著特性（持久性、温度补偿和携带）在从细菌到哺乳动物的所有生物体内都是保守的，这些生物体内的昼夜节律行为已经被观察到。这一原理鼓舞了人们的希望，即生物化学机制也被保存了下来——如果不是在精确的同源性上，那么至少在时钟的一般成分和组成方面。在这个项目中，揭示昼夜节律振荡器机制的方法集中在最不复杂和技术上最容易接近的生物体上，其中生物钟已被证明：蓝藻，聚球菌属菌株PCC 7942。这种生物的技术优势是它的小基因组，这是很容易操纵的遗传，它的生物发光菌株，这提供了一个高度灵活和方便的系统监测昼夜节律基因表达。这种蓝藻系统为详细的分子/遗传分析和时钟调查提供了极好的工具。该项目将使用该系统来解决生物节律性的三个方面：(i)评估蓝藻从其昼夜节律振荡器中获得的适应性优势，（ii）分析时钟基因产物在中央时钟机制中的作用，以及（iii）表征振荡器控制代谢途径的机制。许多生理和细胞过程，包括睡眠周期、体温维持、体内平衡功能、基因表达、细胞分裂和酶活性，都受到生物钟的调节。此外，这些时钟也是植物和动物生殖过程光周期计时中测量日长度的计时器。生物钟的生化机制具有重要的生物学意义；了解它可能会带来在许多方面对社会有用的见解。

Organisms at all levels of biological complexity manifest circadian (daily) rhythms which are controlled by an endogenous biochemical oscillator. The biochemical nature of these biological clocks has been elusive, but one principle which has emerged is that their salient properties (persistence, temperature compensation, and entrainment) are conserved in all organisms in which circadian behavior has been observed, from bacteria to mammals. This principle has encouraged the hope that the biochemical mechanism has also been conserved- if not in exact homology, then at least in terms of the general components and composition of the clock. In this project the approach to unveiling the mechanism of circadian oscillators focuses on the least complex and most technically approachable organism in which a biological clock has been demonstrated: the cyanobacterium, Synechococcus sp. strain PCC 7942. The technical advantages of this organism are its small genome, which is easily manipulated genetically, and its bioluminescent strain, which offers a highly flexible and facile system of monitoring circadian gene expression.. This cyanobacterial system provides excellent tools for detailed molecular/genetic analyses and for clock investigations. The project will use this system to address three aspects of biological rhythmicity: (i) an assessment of the fitness advantage that cyanobacteria derive from their circadian oscillators, (ii) an analysis of the roles of clock gene products in the central clock mechanism, and (iii) characterization of the mechanism by which the oscillator controls metabolic pathways.Many physiological and cellular processes, including sleep cycles, body temperature maintenance, homeostatic functions, gene expression, cell division, and enzymatic activities, are regulated by biological clocks. In addition, these clocks are also the timers that measure the daylength in photoperiodic timing of reproductive processes in plants and animals. The biochemical mechanism of circadian clocks is of fundamental biological interest; understanding it may lead to insights which will be useful to society in many ways.