Synthetic biology: is it magic?

What if magic exists but it should be understood from a different point of view? This kind of magic is not learned in Hogwarts but usually in universities or by reading countless articles in scientific journals. Although it might not be as scenic or spectacular, it indeed shares with what we learned from Harry Potter books the fact of being challenging and usually not working in a first attempt. This “magic” is known as synthetic biology.

What is synthetic biology?

Synthetic biology is a field of science that uses the knowledge we have about life to create new biological parts that provide an organism or device with desired properties. Although there is no official definition [1] and every source or scientist can have their own, it is overall accepted that the field emerged as a combination of molecular biology and engineering principles [2, 4]. It will thus apply the “design-test-build” cycle and this approach will help not only to create useful systems, but also to generate knowledge: as the Nobel Physicist Richard Feynman left written on his blackboard at the time of death (1988) “What I cannot create, I do not understand” [3].

The origins of synthetic biology

The fundamentals of such magic sprouted between 1960 and 1970 [2, 5]. Back then, devoted “magicians” discovered some really useful principles about how life functions. One example is genetic regulation [2]: not all the genes are constantly producing their final product (see our post to understand how gene expression works), but their expression is tightly regulated. Genes include a segment of DNA called “promoter” that can control their expression either by activating or repressing them. For example, lac genes produce proteins that will metabolize lactose and will be expressed whenever the bacteria detect the presence of lactose, but only then, as it would cost too much energy to constantly produce them. Another important tool are restriction enzymes [5], since some of them allow to cut a segment of DNA in a specific point leaving complementary extremes that can match like the pieces of a puzzle.

This background was a key point. We know that different genes code for products with diverse functions (e.g. a fluorescent protein, an enzyme that degrades plastics or a hormone required for the proper functioning of our body), and new genes and functions are still being discovered. Being able to combine those genes and control their expression as desired offers many possibilities to create useful properties that do not exist naturally. That should be magic, right?

In the year 2000, the first genetic circuits appeared, bringing a new era of synthetic biology [5] that has been even considered as the foundation of the field [2]. A good example is the “repressilator”, [6] which is one of the most basic tricks, but still essential to become a good wizard. Basically, it is composed of three genes combined in such a way that the expression of one gene will inhibit the expression of the following one. This triangle of inhibited expression will give an oscillatory pattern of expression that can be useful for many reasons, such as imitating the circadian rhythm. Since then, a wide variety of other genetic circuits have been implemented, inspired by this and other basic circuits and taking advantage of newly developed parts and functions. All that will be soon discussed in an upcoming post.

EXAMPLE OF THE REPRESSILATOR FROM [2]. THE PROTEIN TETR WILL INHIBIT THE PROMOTER OF THE EXPRESSION OF LACI. LACI WILL INHIBIT THE EXPRESSION OF CI. CI WILL INHIBIT THE EXPRESSION OF TETR. AS A RESULT, THE THREE PROTEINS WILL HAVE AN OSCILLATORY PATTERN OF EXPRESSION. IF WE EXPRESS THE FLUORESCENT PROTEIN GFP UNDER ONE OF THE THREE PROMOTERS, WE COULD DETECT THESE OSCILLATIONS.

SBOL USES SIMPLE GRAPHICAL REPRESENTATION OF DIFFERENT GENETIC ELEMENTS [1]

An important pillar of synthetic biology is standardization [4], so the different developed parts (e.g. DNA sequences) are compatible with each other and can be characterized, combined in modules, and shared with higher efficiency. Also, the graphical representation of biological circuits has been standardized thanks to Synthetic Biology Open Language (SBOL) [1].

Applications

You might be wondering which kind of more advanced magic tricks can be done with synthetic biology. The list is almost endless, so long hours of study await you if you want to master this “dark” science; here, some examples of applications will be introduced.

Several synthetic biology contributions have improved medicine and human health. One of the most significant contributions was designed to improve the treatment of malaria, a disease that causes over 400’000 deaths annually worldwide [7]. One of the most efficient medications against malaria is artemisinin, produced by the plant Artemisia annua. The pathway to produce artemisinin was engineered first, partially, in the bacteria E.coli [8] and then, an optimized version, in the baker’s yeast S. cerevisiae [9]. As a result, the time and cost required to produce artemisinin were reduced.

EXAMPLE OF THE PATHWAY TO SYNTHESIZE ARTEMISININ, WITH THE IMPLEMENTATION IN YEAST SQUARED IN BLUE. SOURCE [9]

Another domain where synthetic biology can prove its usefulness are environmental issues. As you might know, fossil fuels are highly polluting and limited, so biofuels can be an alternative to replace them. However, most current biofuels such as bioethanol are derived from sugar cane or corn, which implies a heavy agricultural burden and can put Food Security at risk. Thanks to synthetic biology and microorganisms, the production of more efficient biofuels such as biobutanol can be achieved [1 0].

In the last decade, synthetic biology has increased its pace and scaled up significantly [2], which has allowed for the synthesis of whole genomes, i.e. all the genetic material of an organism. For instance, the genome of different bacteria has been synthesized [1 1, 12], and the next step, the synthesis of a yeast genome, is being attempted [13]. The interesting part of building a whole genome is that the designer can introduce new properties and tools to ease its manipulation, helping to generate more knowledge and useful applications.

Finally, thousands of applications of synthetic biology have been developed in the iGEM competition (see our post), where students from all around the world join their forces and “magical” knowledge trying to tackle current global or local challenges.

Conclusion

So far, we have seen some of the uses of synthetic biology that can make a difference. However, exactly as with magic, great power comes along with great responsibility. For this reason, the analysis of the ethical and social implications of synthetic biology is of huge relevance and there are different institutions involved in such tasks [14].

So, now that you know what magic is, it is up to you to become a wizard. Just one last tip: the wand will be a pipette instead.