Mathematics reveals mechanism for sustaining robust biological rhythms.
In collaborative work, a KAIST mathematician has used modeling efforts to predict the design of a biological circuit that generates robust rhythms. These mathematical modelling methods and predictions are based on differential equations and stochastic parameter sampling. Based on this design, the lab of Professor Matthew Bennett (Rice University) constructed strains of bacteria using synthetic biology and found that they generate surprisingly robust rhythms under various conditions.
Various types of clocks in our body generate rhythms with periods ranging from seconds to days. Our hearts beat virtually every second; and cells divide periodically. The circadian clock located in the hypothalamus generates 24 h periodic rhythms, allowing for the timing of our sleep and hormone release. How these clocks generate and sustain the stable rhythms that are essential to life is a fascinating topic and can be explored mathematically and experimentally (synthetically).
The top-down research approach, which focuses on identifying the components of biological circuits that generate rhythms, while important space, can actually serve to limit our understanding of the mechanisms underlying these rhythms. Synthetic biology, a rapidly growing field at the interface of biosciences and engineering, instead uses a bottom-up approach. Synthetic biologists can create complex circuits out of simpler components; some of these new genetics circuits can oscillate. As electrical engineers can understand a circuit they construct out of batteries, resistors, and wires, so synthetic biologists can better understand biological circuits which they put together using genes and proteins. However, due to the complexity of biological systems, experiments and mathematics need to be used hand-in-hand to design these biological circuits and understand their function.
In this research report, a fruitful interdisciplinary approach revealed that a novel biological circuit can generate robust rhythms. Specifically, Kim’s mathematical analysis suggested (and experiments confirmed )that the presence of additional negative feedback loops, in addition to a core transcriptional negative feedback loop can lead to robust rhythms in this system. This result provides important clues about the fundamental mechanism of robust rhythm generation in biological systems.
Furthermore, rather than constructing the circuit inside a single bacterial strain, the circuit was split amongst strains. When the strains were grown together, the bacteria exchanged information, completing the circuit. Thus, this research also shows how complex biological systems can be controlled by regulating how individuals, within the system, influence each other (e.g. gut microbiome in humans).
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Chen, Ye, et al. “Emergent genetic oscillations in a synthetic microbial consortium.” Science 349,6251 (2015): 986-989.
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