Oscillator Control of Cell Division Cycles in Euglena

点击翻译按钮获取中文摘要

Among other mechanisms that have been proposed to control microbial cell division cycles (CDC), autonomous biological oscillators, ranging from those of the relaxation type to those having limit cycle dynamics, provide a possible means of integrating the disparate concepts of cell cycle transit, exit and arrest. The long-range goal of this research is to determine the nature of the oscillator(s) presumed to couple to the CDC and to generate periodicity of division and other CDC "landmarks" (as well as to underlie circadian rhythmicity in general). As a working hypothesis, based in part on recent findings in the algal flagellate, Euglena gracilis, it has been proposed that NAD+, the mitochondrial calcium transport system, calcium-calmodulin, NADP+ phosphatase and NAD+ kinase, and, perhaps, cAMP together could constitute a light-entrainable, self-sustaining circadian oscillator. These elements would comprise "gears" of the clock underlying the overt rhythm of cell division (and other variables, or "hands") in eukaryotic microorganisms. The approach initiated during earlier work on this project will be continued. First, it will be ascertained whether each successive element of this proposed control loop exhibits circadian rhythmicity in cultures of wild-type Euglena and of an achlorophyllous mutant maintained under free-running conditions (both in the presence and absence of the well documented rhythm of cell division). Then, in order to determine whether each element represents a "gear" of the clock, pulses of various drugs and chemicals which are known to affect these elements will be applied. Direct activation as well as inhibition should each generate phase shifts in the biochemical rhythms and in the division rhythm. Particular emphasis will be given to NAD+ kinase, calcium, and cAMP--putative clock elements that have already been explored in some detail. Ultimately, the goal will be to delineate the coupling links between the oscillator and the CDC regulated by it. The goal of this research is to delineate the biochemical steps proposed to be the components of a circadian oscillator that may underlie the rhythm of the cell division cycle in the green alga, Euglena.