The rising and setting of the sun causes dramatic oscillations in light and temperature. Organisms from bacteria to humans involuntarily anticipate these daily swings by means of an endogenous clock called the circadian clock. At the heart of the clock is an oscillator, which generates a ~24-h biochemical rhythm. This rhythm has a profound influence on metabolism, reproductive fitness, health, and disease. Yet, the molecular mechanisms of circadian oscillators remain elusive. Due to the pervasive importance of circadian rhythms to life on earth, this major gap in knowledge has a broad impact on the field of life sciences.
The central focus of my laboratory is to fill in this major gap in knowledge by elucidating the timing mechanism of the circadian oscillator of cyanobacteria. Recently, we made some exciting findings that were highlighted by Current Biology, Chemical & Engineering News, PNAS, and Nature Reviews Microbiology (2012, 2017).
The oscillator of the cyanobacterial clock is composed of only three proteins: KaiA, KaiB, and KaiC. When mixed together in a test tube with ATP, they generate a self-sustained circadian rhythm for several days. Below is real-time fluorescence data collected by graduate student Joel Heisler on a mixture of KaiA, KaiB, KaiC, and ATP, where KaiB was labeled with a fluorophore:
Our objective is to develop a comprehensive understanding at atomic resolution of how a simple mixture of these three proteins keeps time.
Below is Dr. Archana Chavan's real-time NMR spectra (collected on our 600 MHz spectrometer) where she can observe individual atoms within these clock proteins as they move to tell time (the pink and green traces are of intensities of two peaks over a span of 5.5 days):
Students and postdocs use an array of biochemical, chromatographic, and spectroscopic techniques to test hypotheses formulated on our foundation of existing knowledge and new preliminary data. To see a short cartoon created by undergraduates at UCSD that summarizes work by our lab click the link below: