Dr. Orie Shafer has worked on the neural basis of circadian timekeeping for two decades. He began working on the Drosophila clock neuron network in 1999 and his first interests were centered on the operation of the molecular circadian clock within the neurons responsible for driving sleep/activity rhythms. Before this work, the operation of the well-known circadian feedback loop had been studied largely if not exclusively in biochemical extracts or non-rhythmic cell lines. Early in his career he became interested in the anatomical organization of the fly’s clock neuron network and made significant contributions to this area of study, including the recognition of new subclasses of clock neurons in the fly brain. Upon learning of the development of genetically encoded sensors for neural activity and intracellular signaling, he began to shift his focus from the anatomical basis of circadian timekeeping to the physiological mechanisms underlying clock neuron network function. As it became clear from beautiful work done on the mammalian clock center that circadian timekeeping was a network property of the brain, he became convinced that the ability to interrogate the network connections within the clock neuron network would be critical to the progress in understanding circadian timekeeping and entrainment. His group therefore developed a method of network interrogation that has allowed his team to address the nature of connectivity between clock neuron classes. This approach continues to provide unique insight into clock neuron network function that is directly relevant to the understanding of mammalian clock centers. Shafer’s group has established a consistent record of significant contributions to our understanding of circadian timekeeping in the brain as reflected their publication record in highly respected journals and funding from both the National Institutes and Health and the National Science Foundation.
Dr. Shafer’s research interests focus on circadian timekeeping, the entrainment of circadian rhythms, and the neural mechanisms that support them. Most organisms maintain daily rhythms in gene expression and physiology that are driven by an endogenous timekeeping mechanism called the circadian clock. Such clocks persist in the absence of time cues from the environment with a period that is slightly longer or shorter than the 24-hour period of the solar day but readily synchronize with the solar day when exposed to such time-cues, a process called entrainment. The most familiar circadian rhythm is that of the sleep/wake cycle in animals. The master circadian clock controlling sleep/activity rhythms resides in the brain and consists of networks of diverse clock containing neurons that ensure the emergence of a central circadian rhythm that is robust yet entrainable. An understanding of the neural basis of circadian rhythm generation and the entrainment of circadian rhythms to environmental time-cues is a central challenge and goal of chronobiology. Understanding how these processes operate within modern light and social environments will be necessary to address the widespread and negative consequences of the disruption of the circadian clock and sleep rhythms that accompany modern life. Dr. Shafer’s research program seeks to understand the neural basis of circadian timekeeping and entrainment in the brain of the fly Drosophila melanogaster, a model system that continues to inform and enrich our understanding of circadian timekeeping in mammals, including humans.