Clock in the Cell
Project leader: Dr. Cornelia Madeti
The circadian clock represents a fundamental aspect of biology that is possibly common to all cells. The clock imposes a temporal structure on processes from gene expression to behavior. Clocks are virtually always found in the entrained state in nature. Entrainment is the process whereby the circadian machinery is stably synchronized to the 24h environmental cycle. Entraining stimuli (zeitgebers) include light and numerous other reliable and predictable features of the environment stemming from the light cycle (e.g. temperature, food, etc.). Due to genetic and environmental variability (e.g. season), a distribution of entrained phases or chronotypes is observed in a given population. Thus, entrainment is not a single entity but rather a dynamic process and until we have figured out the rules therein we cannot understand daily timing.
We aim to elucidate the rules of entrainment using a novel approach, namely by describing and probing intracellular molecular oscillators. The clock in the organism is an amalgam of so-called peripheral clocks, such as liver, eye, kidney and heart. The human circadian clock is a combination of these organ oscillators, as they synchronize with the clock in the brain. However, each of these peripheral clocks is built from individual cells and thus it is the clock characteristics of cells that ultimately determine clock characteristics of the organism. For this work, we exploit the simplest cellular clock systems for this work: Neurospora crassa, human U2OS cells, S. cerevisiae.