An artificial molecular clock to control artificial molecular machines

One of the challenges in developing advanced nanotechnology, sometimes called molecular manufacturing or productive nanosystems, is learning to control systems of molecular machines by using other molecular systems for timing and turning machines on and off. The more complex the desired output of a molecular machine system, the more different kinds of molecular machines that need to be controlled, and therefore the more complicated the problem of control systems. A molecular system to time molecular motion and production has been demonstrated by a team of scientists that includes Erik Winfree, co-winner of the 2006 Foresight Institute Feynman Prize in both the Theoretical and Experimental categories. The research was published in the Proceedings of the National Academy of Sciences [abstract, Open Access PDF]. A description of the research published in Biopolymers is available on Winfree’s web site. Another description is available on the Human Frontier Science Program web site.

One of the professed goals of this research was to advance understanding of the complex regulatory networks that need to be constructed in synthetic biology by building simpler regulatory networks, with reduced number of components, using biochemical circuits that work in the test tube. However, this same understanding should prove useful for building control circuits for productive nanosystems as well. The current demonstration is based upon a synthetic transcriptional oscillator [Open Access] published by two of these authors earlier this year. The transcriptional oscillators consist of two enzymes (one that synthesizes RNA and one that degrades RNA, and a number of DNA molecules that serve as genes for producing small RNA molecules that switch those genes either on or off. Consequently, the oscillator is based upon “genelets” that produce regulatory RNA molecules. Three different oscillators exhibiting both positive and negative feedback control were demonstrated.

In the current work, the authors use such a transcriptional oscillator as a molecular clock to time two other molecular processes. One of these is a DNA nanomechanical device, a DNA tweezers that gives different fluorescent signals when open and when closed. Different RNA molecules produced by the transcriptional oscillator act to either open or close the tweezers. The other process is the synthesis by the transcriptional oscillator of an RNA molecule that binds the dye molecule Malachite Green, changing its fluorescence.

The regulatory circuits worked, but the detailed behavior turned out to be complex. Regulation was found to be improved by the introduction of an additional “insulator circuit” to produce an amplified signal. Many details need to be worked out even for relatively simple systems, but these results are first steps toward designing and implementing controllable molecular machine systems.

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