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.
