Christian I. Hong, PhD
Our lab is interested in the molecular mechanism of circadian rhythms and its functional role in cell cycle controls. Circadian rhythms are periodic physiological events that recur about every 24 hours. The importance of circadian rhythms is well recognized in many different organismsí survival as well as in human physiology. Misregulation in circadian rhythms may lead to different conditions such as depression, familial advanced sleep phase syndrome (FASPS), delayed sleep phase syndrome (DSPS), and/or insomnia, which largely impact our society. Recent studies indicate higher incidents of cancer in clock defective mice and chronic jet-lag is associated with higher mortality rate in aged mice. The cell cycle control is intertwined with circadian network via molecular coupling factors such as WEE1, a kinase that is involved in G2 to M transition. Therefore, maintaining robust circadian rhythms is vital for the health of an organism.
Circadian rhythms are dictated by cellular regulations of transcriptional and translational feedback loops. There are positive and negative elements that create a time-delayed negative feedback loop to generate a rhythm of about 24 hours. Several core clock components oscillate in terms of their quality and abundance, and determine the period and the phase of the circadian clock. We use mathematical models and tools in genetics and molecular biology to investigate molecular components and dynamical properties of circadian rhythms and cell cycle in a model organism, Neurospora crassa. Neurospora is a filamentous fungus that provides excellent tools for circadian rhythms research. We follow molecular rhythms in real-time with bioluminescence assay utilizing luciferase derived from firefly luciferase. We can track gene regulations or protein abundances as a function of time with bioluminescence assay. This provides a good handle for us to study dynamical properties of circadian rhythms and cell cycle in various genetic backgrounds. Hypotheses are derived from mathematical simulations and predictions are experimentally validated. This interdisciplinary approach creates a synergy to efficiently understand nuts and bolts of circadian rhythms and its roles in cell cycle control.