Chronobiology and Neuroscience
Research in the Cassone laboratory is directed at the mechanisms and neuroendocrine pathways by which the biological clock regulates physiology and behavior in vertebrates, especially in birds. All eukaryotic and at least some prokaryotic organisms express a temporal organization as well as a spatial organization such that many molecular, physiological and behavioral events are strictly timed. This temporal organization reflects a biological clock derived primarily from endogenous cellular oscillators that are somehow coupled or entrained to the prevailing environmental cycles. Recently, we have become interested inmechanisms by which the circadian clock regulates gastrointestinal function. Part of this research has revealed an enteric bacterium, Klebsiella aerogenes, that exhibits a circadian rhythm in swarming behavior and gene expression. We are investigating the mechanisms that generate circadian rhythms in this bacterial organism. Students in the laboratory are encouraged to develop independent projects based upon scientific questions within the framework of the laboratory's mission. Weekly lab meetings and personal supervision of laboratory projects help to integrate technically diverse but philosophically intimate graduate and undergraduate research.
Functional Genomics of the Avian Circadian Clock: The avian pineal gland is a circadian oscillator and photoreceptor, which regulates birds' physiology and behavior via the secretion of the hormone melatonin. While the molecular mechanisms underlying melatonin biosynthesis have been largely worked out, the molecular clockworks regulating circadian rhythms, the photoentrainment of these rhythms to environmental light cycles and the link of the oscillators and photoreceptors to rhythmic outputs. We are studying the mechanisms by which molecular clockworks regulate these physiological outputs ranging from metabolism to complex behavior.
Circadian and Seasonal Regulation of Bird Song: Bird song is one of the few non-human forms of syntactical and contextual of animal communication. Bird song is regulated by a complex of brain structures collectively called the "song control system". We have found that song control brain structures express melatonin receptors and that bird song behavior and bird song control structures are regulated on a daily and seasonal basis by pineal melatonin. We are studying the mechanisms by which melatonin and the circadian system synchronizes bird song to the time of day and the time of year. We are also interested in mechanisms by which bird song itself may feed back on circadian sleep/wake cycles in birds.
Circadian Regulation of Gastrointestinal Function: We have established that there is a semi-independent circadian oscillator within the gastrointestinal system. This system is synchronized to external time through the action of the hypothalamic suprachiasmatic nuclei (SCN) , which communicate to peripheral organs through the sympathetic autonomic nervous system. Our current interests involve investigations of other modulators of gastrointestinal rhythmicity and of the impact of circadian clocks on diseased states and normal aging.
Circadian Clocks in a Gastrointestinal Bacterium: We have discovered a human gastrointestyinal commensal bacterium that is sensitive to the hormone melatonin and that expresses a circadian rhythm in swarming behavior and gene expression. The circadian rhythm of this bacterium can be entrained to the very small 1 degree fluctuations in body temperature and is synchronized by the presence of melatonin. We are studying the molecular mechanisms of this prokaryote clock in vitro and in situ within the gastrointestinal tract of laboratory mice.
