Interrogate and Design a Biological Clock

View all posters

Sen Liu, Song Liu, Weiqun Chen, Pei Dong, Chenzeng Liao

China Three Gorges University, China

Precise timing is important for many people in our daily life, and it’s also extremely important for nearly every biological process at the molecular level. In accordance with the day/night switch on earth, biological behaviors are generally guided by a 24h rhythm. In human and eukaryotes, this rhythm was believed to be governed by transcription-translation-feedback loops (TTFL). However, it was shown in the last two years that non-TTFL biological clocks also exist in human and other eukaryotic cells, although the detailed molecular mechanisms are pending to be elucidated. Therefore, we are using a non-TTFL clock, the KaiA/KaiB/KaiC clock from blue-green algae, as a model to study the basic mechanism. As the only known protein-protein interaction based biological clock, the KaiA/KaiB/KaiC oscillator can be fully reconstituted in vitro. Combining computational and experimental methods, we’re interested to know what parameters are deterministic for this protein-based molecular clock, and how to design an orthogonal clock from this one, how to modulate this clock with artificial inputs, and how to output signals from this clock. We have identified some critical residues at protein-protein interfaces, and designed a light-modulatable protein, as well as a starting network model. We will interrogate the clock with our designs, incorporate our experimental data in the network model, and hopefully predict new behaviors and parameters from optimized models.