Circadian rhythm disruption, as experienced in shift work, nocturnal light exposure, and aging, is a serious risk factor for disease, including cancer, diabetes, obesity, and cardiovascular and neurodegenerative diseases. As we learn more about the circadian system, it is becoming clear that these disruptions arise not only from shifts in the clocks of individual organs, but also from disruptions of the complex interactions among the clocks of different organs. To study these interactions at a system level, we have developed a method to measure circadian rhythms in specific organs of living animals. We will apply this method to address a fundamental unresolved question in the application of chronobiology to health: By what method can we optimize entrainment of the entire circadian system to shifted light signals? Using our method of in vivo, molecular, organ-specific detection of rhythm in behaving animals, we will search for new methods of resetting the clock that maintain phase alignment among clock components. In parallel, we will continue to develop new approaches for the study of circadian rhythm dynamics in vivo.
Our first aim i s to measure the entrainment dynamics of liver and brain suprachiasmatic nuclei (SCN) in response to an advanced light cycle. We will then determine if timed food availability can serve to shift the liver faster so that is does not lag behind the shift of the SCN. Undergraduate students at the largest US women's college, Smith College, will conduct this research. Through a multifaceted program with documented success, we will recruit 1st-year students from under-represented minority groups and engage them in hands-on scientific research, with engaged mentorship. Student research teams will include majors with strong quantitative training (e.g., statistics and data science, engineering) and results will be shared via our lab site on the Open Science Framework. Students will be involved in all aspects of the research and will present results at conferences and contribute to publications.
This research extends new molecular methods for measuring jetlag in behaving animals. We will determine how we can reduce internal phase misalignment associated with jet lag by measuring circadian rhythms from the liver using a transgenic mouse and newly developed substrate molecules and imaging equipment. This research will help us develop better advice for people with jobs or diseases that disrupt daily rhythms, a risk factor for metabolic and cardiovascular diseases.
