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Engineering Life

by Lawrence Zeldin, Ben Liu, Tom Suh, and Suyasha Shrestha

As our knowledge of biological systems has progressed through the years, it has become increasingly clear that the magnitude of complexity found within a simple cell is greater than that of any contraption that humans could ever create from scratch. While the idea that we could never mimic nature has be ingrained in our minds for years, new breakthroughs in synthetic biology are slowly beginning to chip away at this idea.

Synthetic biology is a new and rapidly developing field that seeks to apply computational and electronic concepts in the engineering of novel biological pathways. These pathways, while still using components found in natural cells, use components in novel ways devised by researchers. For instance, existing signaling pathways can be modified to detect new environmental factors, or to cause the expression of a new gene introduced into a cell. Synthetic biology also seeks to bridge the gap between biology and technology, and a focus of many researchers is to mimic electronic devices with biological mechanisms.

In the article Synthetic biology: applications come of age, researchers discuss several novel methods of mimicking contemporary electronic circuit functions using the biological mechanism of the various cells. One such method involves the use of gene expression and repression. In order to mimic electronic switches within a cell, researchers engineered a system of two genes, each controlled by its own promoter. The products of each gene repress the promoter of the other, so once one gene is being expressed, the other becomes dormant. The cell can only switch state with external stimulus, making this a stable switch. In order to mimic an oscillator, researchers used three genes that each inhibited the next in a cyclic pattern. This created a predictable pattern of expression that could be used to track time.

In order to control these genetic mechanisms, the next step was to integrate a way for the cell to sense its surroundings. Two methods were developed. One uses antisense RNAs, which can bind to and repress mRNA molecules. These repressor RNA’s only become active in the presence of a specific ligand molecule. A similar concept is used with receptor proteins, which can be engineered to affect gene expression when they bind to certain molecules.

In the article Realizing the potential of synthetic biology, researchers George M. Church, Michael B. Elowitz, Christina D. Smolke, Christopher A. Voigt and Ron Weiss discuss the achievements, future applications, and challenges of synthetic biology. Synthetic biology, which first focused on programming bacterial cells with basic circuits has now expanded to programming complex multicellular systems into a variety of different organisms. Synthetic approaches can now be used to carry out a variety of biological functions such as metabolism and development. However we still have little understanding of how synthetic models can function effectively in cells. Some of the main challenges include safely delivering synthetic circuits into mammalianorganisms and coordinating systems on a multicellular level. Development in these areas can allow us to create effective applications such as cancer therapies and engineered tissues.

Today, more and more scientists envision a brighter future enhanced with biosynthetics: microorganisms converting waste into biofuels as renewable energy, remedial bacteria that attack cancer tumor cells, and phage therapies that target undesired antibiotic­resistant bacteria. Surely effective methods that directly aid multicellular organisms have not been perfected, but with developing mechanisms such as mimicry and receptor proteins, synthetic biology may not be far from treating the biggest concerns of humanity.

Ahmad S. Khalil and James J. Collins, Synthetic biology: applications come of age. Nature Reviews Genetics 11, 367–379 (2010) doi:10.1038/nrg2775

George M. Church, Michael B. Elowitz, Christina D. Smolke, Christopher A. Voigt and Ron Weiss, Realizing the potential of synthetic biology. Nature Reviews Molecular Cell Biology 15, 289–294 (2014) doi:10.1038/nrm3767

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