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Synthetic biology: what industrial prospects?

上海交大巴黎高科评论  · 公众号  ·  · 2016-09-19 16:39

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The American botanist Luther Burbank then started to compare plant breeding to “architecture.” Stéphane Leduc, a French physician from Nantes, introduced in 1921 the term “synthetic biology.” The synthetic method, he wrote, “seems to be the most fruitful, the most likely to reveal to us the physical mechanisms of life phenomena whose study is not even sketched.”

However, it was not until the 1950s and 1960s that synthetic biology began to be considered from a technical point of view, through the development of such tools as the electron microscope that enabled dramatic advancement in the understanding of biology at the molecular level: among these is the discovery of DNA in 1953.

Meanwhile, it appeared more and more obvious that even though evolution works randomly, mathematical principles ruling biological networks are discernible. Then at the end of the 1990s, the rise of the biology of the systems offers a fertile ground which a number of engineers began to focus their attention on. Their motto: What I cannot create, I do not understand, a famous saying from physicist Richard Feynman, heard during one of his lectures at Caltech.

At the turn of the century, Drew Endy and Tom Knight laid the foundations of synthetic biology as we know it today. iGEM, the student competition they launched in 2004, proved crucial for the development of synthetic biology and contributed to the latter being introduced in France in 2007 at the Centre for Interdisciplinary Research in Paris. It is by participating in this competition that many researchers were introduced to this emerging field.

Proponents of synthetic biology introduced in molecular biology a number of principles directly inspired from engineering: modularity, standardization and abstraction. The concept of “BioBrick,” a standardized DNA sequence easily reusable and presenting a characterized behavior, being an emblematic illustration.

Small living factories

Synthetic biology is both Cartesian and reductionist. But too radical a simplification of biology can lead to overlook some of the “tricks” found by living organisms in the hundreds of thousands of years of development, tricks that would teach us interesting lessons.

Living organisms are remarkably effective. For example, the cell components are strictly organized in space, with a diversity of compartments called organelles. Many bacteria specialize these micro-compartments in certain metabolic reactions, thus increasing the productivity of the relevant enzymatic pathways. One can easily understand how interesting it would be to artificially control the spatial organization of these metabolic pathways.

This is where DNA nanotechnology comes in. This area uses the DNA bases complementary to design sequences assembling in an orderly manner at the nanoscale, in predefined patterns: nanowires, structures in two or three dimensions. Would it be possible to use the knowledge of this science to build artificial “organelles” to isolate any metabolic pathway and thus increase accuracy and performance?

Building a bridge between nanotechnology and synthetic biology is not an easy task. First, DNA nanotechnologies were previously only test tube science. How to manage simultaneously all the assemblage principles acquired in this field by 20 years of in-vitro experimentation, to make it work in-vivo? Then, how to work with RNA instead of DNA? RNA can be produced in large quantities in bacterial cells but poses a stability problem. Finally, how to characterize these structures in vivo? When venturing on the unpaved roads of science, new techniques for exploration often have to be developed.






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