Oscillatory timeseries data sheds light on mechanisms underlying circadian timekeeping

The circadian clock generates ~24h rhythms everyday via a transcriptional-translational negative feedback loop. Although this involves the daily entry of repressor molecules into the nucleus after random diffusion through a crowded cytoplasm, the period remains extremely consistent. In this talk, I will describe how we identified a key molecular mechanism for such robustness of the circadian clock against spatio-temporal noise by analyzing spatio-temporal timeseries data of clock molecules. Furthermore, I will illustrate a systemic modeling approach that can identify hidden molecular interactions from oscillatory timeseries with an example of a circadian clock and tumorigenesis system. Finally, I will talk about a fundamental question underlying the model-based time-series analysis: “Can we always fit a model to given timeseries data as long as the number of parameters is large?”. That is, is Von Neumann’s quote “With four parameters I can fit an elephant, and with five I can make him wiggle his trunk” true?