Ph.D. 2009, University of California, San Francisco
Postdoctoral Fellowship 2010-2015
University of Pennsylvania Perelman School of Medicine
To ensure optimal survival, organisms have evolved an endogenous timing mechanism, called the circadian system, which allows them to anticipate and adapt to the daily cycles of light and temperature caused by the rotation of the Earth on its axis. The ability of organisms to keep time depends on a population of brain cells called clock neurons, which each contain a cell-autonomous molecular clock. Even in the absence of external signals such as light and dark, these cells tick away with a cycle of ~24 hours and communicate with other brain regions and peripheral tissues to synchronize many diverse physiological and behavioral processes with respect to one another and the external environment. Because of its ubiquitous involvement in many important functions, it is not surprising that disruptions of the circadian system, such as those that occur with shift work or as a result of the aberrant sleeping and eating schedules common in modern society, can cause severe metabolic and cognitive deficits in diverse organisms, including humans.
The circadian system can be divided into three components; in addition to the clock cells, which keep time, there are input pathways that transmit environmental signals to the clock, and output pathways that couple the clock to behavioral and physiological outputs. These components form a complex network of cells and circuits that together generate rhythms. Though much is known about the molecular components of the circadian clock, as well as the identity of the core clock neurons, the downstream neuronal populations that comprise the circadian output pathway remain largely undefined, and thus fundamental questions remain about the ways in which the circadian clock cells control behavioral and physiological outputs. For example, what are the neuronal circuit mechanisms through which the circadian clock connects to multiple distinct behavioral outputs? What are the genes and molecules used by neurons of the output circuit to control behavioral and physiological outputs? How do cells of the output circuit, which often lack molecular clocks, transmit circadian information? My research uses the fruit fly, Drosophila melanogaster, to delineate the genes and circuits that couple the circadian timing mechanism to overt behavioral and physiological outputs such as sleep, locomotor activity, and feeding behavior. I am also interested in investigating the interaction between the circadian and stress response systems and identifying the behavioral and cognitive consequences of circadian disruption. I take a multi-faceted approach, combining state-of-the-art genetic, neuroanatomical, and behavioral techniques, including thermogenetic activation and inactivation of neurons, live functional imaging of neuronal activity, single-cell RNA sequencing, immunohistochemistry, and confocal microscopy. This line of research satisfies two major goals that span molecular, cellular, and systems-level neuroscience. The first is to address fundamental questions in the fields of sleep and circadian biology, which have considerable relevance for understanding human function and quality of life. The second, more basic goal is to provide a general framework with which to understand how neuronal circuits function to govern complex behaviors, a question that is at the forefront of current neuroscience research.
More information can be found at our laboratory website: cavanaughlab.weebly.com