Most students and followers of Synthetic Biology will be familiar with the repressilator
(If you’re not a student of Synthetic Biology, you can become one. The Synthetic Biology Community has a strong ethos of open science and you can find course materials on OpenWetWare (including the course I took).)
Towards the end of last year, I blogged about a fast, robust and tunable synthetic gene oscillator and the difference between this oscillator and the repressilator.
In this week’s Nature, another biological oscillator makes an appearance. In contrast to the two aforementioned synthetic biological oscillators, this one is constructed in mamallain (CHO) cells. Again a different circuit design is used – this oscillator makes use of sense-antisense transcriptional control to construct positive (using the sense strand) and negative (using the antisense strand) feedback loops.
The accompanying News and Views article considers how in silico and in vivo studies have made apparent the role of positive and negative feedback loops in biological oscillators. The authors of the News & Views article draw parallels between our current understanding of biological oscillators and the seventeenth century’s replacement of the water clock with the pendulum. The say
Advances in generating biological oscillations are similar to those made in the seventeenth century that led to our widespread adoption of the pendulum clock.
Is this an optimistic view of the current state of our understanding? Together, the three papers I mention here describe improvements including new and more detailed mathematical models and the design of more robust, tunable oscillators. However the heritability of the oscillations between parent and daughter cells is partial and the oscillations die out over time.
I was not around in the seventeenth century to witness the establishment of the pendulum clock as the de facto standard for timekeeping, so I cannot say whether the current stated of play in Synthetic Biology is analogous with the progress and pitfalls of the first pendulum clocks. Synthetic biology has plenty of scope for learning from mathematical models and natural oscillators (such as those that track circadian rhythms). But since their invention in the seventeenth century, pendulum clocks have been replaced with atomic clocks, and whilst natural oscillators are remarkable in their robustness to variation in extrinsic conditions, it will be a long time before we establish a Synthetic Biological clock with the precision demanded by today’s time keepers.
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Marcel Tigges, Tatiana T. Marquez-Lago, Jörg Stelling, Martin Fussenegger (2009). A tunable synthetic mammalian oscillator Nature, 457 (7227), 309-312 DOI: 10.1038/nature07616
