But what was the time? – where was a clock? Virginia Woolf, Mrs. Dalloway
In animals the timekeeping necessary for sleep/activity rhythms takes place within neurons located in discrete regions of the central nervous system (CNS). Remarkably, neuronal circadian clocks can maintain molecular and physiological rhythms in the absence of time-cues from the environment or other cells. Despite such cell-autonomous timekeeping, the orchestration of daily behavioral rhythms depends on networks of clock neurons. Work in the Shafer lab seeks to understand the circuit properties of these networks and to examine the roles that identified neurons play in the control of circadian rhythms. We use anatomical, genetic, and live-imaging techniques in the fly Drosophila melanogaster to discover how time is kept within the brain and how it is used to orchestrate daily and seasonal changes in behavior.
The Drosophila brain consists of approximately 100,000 neurons, around 150 of which express a molecular circadian clock. The anatomy of these neurons, their targets, and their relationships with sensory inputs are one focus of our research.
The discovery of clock genes in Drosophila changed the way we think about the genetic basis of behavior. The study of these and other behaviorally relevant genes has established that single nucleotide changes in identified genes can have significant effects on behavior, even in humans. The Shafer lab is interested in how gene function ripples through the complex neural circuitry of the brain to contribute to animal behavior. To that end we manipulate gene function within identified neurons in the fly brain to understand where clock genes are required for the normal control of behavioral rhythms. In doing so we hope to integrate the anatomical and genetic basis of timekeeping.
The considerable genetic tools available in Drosophila make it possible to manipulate gene expression and cell function with remarkable precision. However, the small nature of the fly’s CNS and the inaccessibility of most of its neurons to electrophysiological measurement make the physiological analysis of neuronal networks difficult. The use of genetically encoded, fluorescent sensors of cell signaling have made it possible to conduct physiological investigations within genetically defined networks of neurons in the fly brain. The Shafer lab uses live imaging methods to investigate the circuit properties of the fly’s clock neuron network. In addition, we are interested in developing new imaging methods for the neurophysiological investigation of neuronal networks that have been implicated in the control of various animal behaviors.
Department of Molecular, Cellular and Developmental Biology
3057 Kraus Natural Sciences
830 North University
Ann Arbor, MI 48109-1048