Research

Overview:

The goal of our research is to understand the mechanisms underlying circadian clock regulation, failure of which may lead to many human pathologies such as cancer, diabetes and heart disease. Life on Earth evolved in the context of a 24-hour recurring environment and many, if not most, aspects of biology are affected by circadian clocks. A fundamental property of these rhythms is their ability to not only to entrain to daily cycles of light and temperature, but also to persist in constant conditions with free-running periods that deviate slightly from the expected 24 hours. We are interested in obtaining fundamental insights into all aspects of circadian clocks: input pathways, output pathways, and core clock regulation. Our approach combines cutting edge cell biology and microscopy techniques, neural activity and circuit mapping tools, and techniques to monitor behavior and metabolic output. Our ultimate goal is to understand how clocks regulate physiological and behavioral processes and to discover new therapeutic targets in the treatment of circadian disorders. 

Temperature, Time, and Sleep Rhythms 

While a lot is known about how light entrains the clock, our recent studies focused on understanding how the circadian clocks set the timing and duration of sleep by integrating environmental temperature cues into its neural network. We are currently investigating: 1) novel circadian thermoreceptors, 2) neural pathways involved in the temperature entrainment of the clock. Our lab is tackling these fundamental problems, which has wide-reaching implications in both circadian and sensory biology, using a wide array of molecular biology, imaging, and neural activity monitoring tools.

Clocks and Metabolism: Fly Calorimeter

In the field of circadian biology, there remains a distinct gap in understanding how rhythmic food intake entrains the clock and the related input and output mechanisms. Recent studies in mice suggest that food cycles function as potent timing cues for peripheral clocks, however, many fundamental questions remain unanswered because of the complexity and heterogeneity of the mammalian circadian system and the scarcity of genetic tools to modify gene expression in a flexible and rapid manner. We seek to investigate the links between food intake, circadian clocks, and metabolism by leveraging the techniques we recently developed that make it possible for the first time to precisely monitor food intake and metabolic rhythms combined with powerful genetic, neural and molecular tools. Elucidating the mechanisms of circadian entrainment will not only lay the foundations for a strong scientific framework, but also provide new opportunities for the development of novel strategies to target clock machinery and treat diseases.