Tripping along the trail to the molecular mechanisms of biological clocks.

Solving the mechanism of circadian clocks has become an important goal, in part because daily rhythms are running in such a wide variety of organisms, and contribute to many aspects of their well being. Systematic genetic approaches to studying 'the clock' were initiated in fruitflies more than 20 years ago as a novel means by which neural-pacemaking mysteries might be solved. Such chronogenetic investigations gained momentum when they spread to other species, and became molecular. However, the molecular studies were misleading, that is, until some elementary neuro-anatomical observations, involving the expression of a 'clock gene' in Drosophila, gave the experiments in this molecular-neurogenetic area of chronobiology a new direction. The initially neuro-descriptive studies led to the current investigations that involve negatively acting transcription factors and other clock molecules that are presumed to interact with them. In addition, new mutants and clones have been isolated in a timely manner. These mutations and molecules should permit chronogeneticists, working on a wide variety of organisms, to unravel further details of how the clock works, how environmental information finds its way to it, and how it sends information out into the organism's physiology, biochemistry and behavior.