Physiological Output Mechanisms of a Molecular Clock

<p>Many organisms exhibit circadian behavior. A familiar illustration of this can be seen in people who have regular sleep habits. Such individuals wake up and become sleepy at regular intervals. Most of our understanding of the molecular mechanisms of circadian behavior has come from the study of Drosophila fruit flies. Although Drosophila and mammals are outwardly very different, the mechanisms that underlie circadian behavior are very similar. Drosophila and mammals both have pacemaker neurons in their brains, and respectively, all pacemaker neurons examined thus far in all animals contain a molecular circadian clock that runs at a roughly 24 hr period. Scientific discoveries in Drosophila are rapidly translated in a cost effective fashion towards understanding similar processes in humans and other mammals. Dr. Holmes's laboratory recently discovered that electrical activity in pacemaker neurons in Drosophila has a much more important role for circadian behavior than suspected previously. While earlier work has shown circadian fluctuations in pacemaker neuron electrical activity, a clear link between the circadian molecular clock and pacemaker neuron electrical activity has not emerged until Dr. Holmes's recent published work. These discoveries provoke a new and exciting set of questions including the question of which proteins are present in pacemaker neurons that might regulate pacemaker neuron electrical activity, and whether fluctuations in pacemaker electrical activity provides a output mechanism for the circadian molecular clock. The broader impacts of this work are far ranging. The Holmes laboratory has developed, and continues to develop a general set of molecular tools in the form of modified ion channels that can be applied to study many other neural circuits. The Holmes laboratory has been responsive to requests from other scientists who wish to use scientific materials that they have developed. Lastly, this work augments the training of students and postdoctoral fellows in the Holmes laboratory, including minority students. </p>