While creating, designing, and manufacturing the tools and apparatus that support day-to-day function, we derive design implementations from many of nature's biological modi. Such examples include Tokyo's rail system, which mirrors the nutrient channels of slime molds, sugar-coated RNA vaccines that mimic tardigrades' defense, and bullet trains inspired by the flight of kingfisher birds. We are inspired in such ways because nature and biology have been performing these groundbreaking feats of engineering for billions of years, much longer than humans.
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Synthetic biologists and biological engineers aspire to control and modulate the sophisticated ways life operates- to adapt certain constraints and expressions that would benefit the individual. The future of these technologies, a field still in its infancy, is the alteration and modification of the genetic code.
Retron Library Recombineering (RLR)
With the readout of the entire human genome came the need to express certain genes and alter the expression or downregulation of certain proteins. CRISPR technologies have shown the most promise when it comes to editing and regulating our genetic code, but what is arguably more important is the way CRISPR paved the way for future advances in bioengineering. Retron Library Recombineering (RLR) is a great example of such an inspired technology.
Similar to CRISPR, the cellular machinery used in RLR was found in bacteria and implemented as a line of defense against viruses. What researchers strive to do, is to replicate this genetic machinery in E. Coli while, at the same time, creating mutant libraries. As a consequence of quick replication via binary fission, the generated libraries will produce millions of different mutants, each corresponding to a different alteration in the genome. If, for example, one mutation leads to the synthesis of an antibiotic resistance allele, we can see how that mutation came about on a genomic level and edit it.
Unlike CRISPR, these Blackbox experiments incorporate a "hypothetical" problem/quandary by allowing us to reach the solution before identifying a target/problem. This practice is somewhat detached from the normal scientific method, though the data it provides could still be fruitful. However, the retrons and other RLR cellular machinery are not expressed well in mammalian cells. Not only that, but growing E. Coli to express just one desired mutation through the retron recombineering system is difficult, with an initial success rate of less than 0.1%.
Examples of Bioengineered Products
Some of the most innovative forms of bioengineering currently being implemented, which see prospective gains in the future, are in agriculture and materials. For example, drought and other abiotic factors are being addressed by engineering microbes, gDNA, and Cas9 templates. This is becoming more and more pressing as global temperatures rise and droughts become more frequent.
While exploring the glycolysis cycle of plant cells, scientists surveyed the role of trehalose and how it plays a role in abiotic stress. They found that this non-reducing disaccharide not only plays a role as a carbohydrate and carbon source but is also a prime osmoprotectant against water scarcity, freezing, salinity, and even radiation. To grow the desired mutation which expresses greater amounts of Trehalose, gRNAs were designed, grown in plasmids, and transfected into the seeds of A. tumefaciens plants, leading to a more durable plant.
Once crops have been harvested further along the food production chain, we see these same technologies being used to create meat substitutes by encoding for heme proteins that mimic the texture and taste of traditional "red meat" products. This has promoted sustainability and health in numerous ways. Firstly, those looking for realistic meat substitutes can now find better products, which will lessen the overusing of land attributed to cattle and pig production (given that 80% of global agricultural land is used for livestock). Secondly, 11% of vegans and 21% of vegetarians have lower levels of ferritin (iron) than is recommended (recommended value is >12 ng/mL), leading experts to believe that this implementation of "heme" in staple crops may yield a healthier lifestyle.
Though most associate bioengineering with food production, cross-pollination between this and materials chemistry exists. We see material akin to leather being fabricated through mycelium and fungi, durable pastes akin to concrete being developed using biomanufacturing operations, and durable wares made from bioengineered spider silk. Though distribution in a scalable manner is still underway, researchers at the School of Engineering & Applied Science at Washington University have been fabricating spider silk that may be stronger than some steel alloys, using only protein-based materials. Due to the cannibalistic and territorial nature of these spiders in nature, bioengineers have offered us a viable counterpart in the form of these 370 kDa proteins. Now, the bigger challenge is to catalog all the potential uses for such a versatile design.
Yet, the dangers and consequences of these emerging technologies should not be masked by the boons they hold. The "dual use" concept in engineering and other sciences deals with the constructive and destructive ends these technologies harbor. Though the potential is great, these concepts can be misused, prone to hazards and accidents, and even weaponized if governmental bodies or other entities choose. For these reasons, bioengineered products are held in very high regard while, at the same time, being handled with the utmost care.
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Continue Reading: The Revolution of Synthetic Biology
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