|Abstraction Hierarchy, as shown
Imagine that we can use living organisms as we use nuts for construction or the transistors in electronic devices. Then we could routinely wire some functions from a given organisms to the functions of another one. It wouldn’t be hard to exchange components across constructed mechanism. It would be even possible to predict a system’s behavior from the knowledge of its parts, just as if they were electronic cards in which a program has been written.
Synthetic Biology has actually that propose: to build controllable devices from living organisms and their molecular components.
Undoubtedly, the central aspects are genes. But, what distinguishes Synthetic Biology from the now classic Genetic Engineering? The main differences are condensed in two concepts: standardization and cuantification.
|Dr. Tom Kinght.
What would happen if, suddenly, all the construction material suppliers decided to produce artifacts with different measures? With everyone producing beams of different size, screws that do not match with the competence materials, or incompatible devices: chaos would emerge! Then, the time required for constructing, let’s say, a decent house, would rise to unprofitable magnitudes. And not to mention what it would be like with the construction of a building!
That is, however, what happened (and still happens in some places) with Genetic Engineering. Each lab “cuts and pastes” genes using different protocols and restriction sites, in such a way that the resulting construction would be more or less like an artisanal production.
For Genetic Engineering to take a step forward in the run to reach the long way already passed by the other classical engineering disciplines (chemical, mechanical, electrical and civil), it was necessary to establish a standard in order to ease the biological system’s construction. In this way, not only more complex projects are enabled, but also quantification, mathematical modeling and design are eased. This is what Synthetic Biology Standards consist of.
One of the first ones, was the BioBrickTM standard, developed by MIT researchers. In a 2003 publication, Dr. Tom Knight proposed the “idempotent” vector system, i.e. vectors with restriction sites that allow successive concatenations without losing the parts concatenated in previous steps. Then, in 2008, in another MIT publication by Dr. Reshma P. Shetty, Dr. Drew Endy and Dr. Tom Knight, this idempotent vector concept was further developed and refined for the construction of vectors and parts, which would ensemble according to specific rules; these rules and standard procedures were called the BioBrickTM standard.
Among the rules of the BioBrickTM standard, the most important are those regarding the need of removing certain restriction sites, which are to be exclusively used in the concatenation process.
There actually is a catalogue of standard parts of DNA: the Registry of Standard Biological Parts, where pieces are also registered following other recognized standards, like the BglBricks, that eases protein domain concatenations.
It is in this Registry where one can find the DNA sequence from gene-promoter regions, ribosome binding sites with different potencies, many different genes, terminator regions, and also already-built constructions and “chassises”, i. e. the living organisms where these bio-parts are to be wired.
The number of registered parts grows each year thanks to the work of laboratories from the whole world, and thanks too to the most prestigious international competition of Synthetic Biology at the undergraduate level: the iGEM.
Thus, using a standard format to concatenate functional DNA, it is possible to conceive the construction of genetic circuits with a huge variety of behavior, which can also be quantitatively assessed and interpreted in order to build a mathematical model with some predictive value. This leads us into the second concept that differentiates Synthetic Biology from the classic Genetic Engineering: cuantification.
|Protein generator diagram:
the green arrow simbolizes a transcriptional promoter;
the green oval, a ribosome binding site;
the purple arrow, an open reading frame;
and the red hexagon, a transcriptional terminator
What kind of constructions can be built with bioparts? Let’s start with one of the most basic: a protein generator. The ingredients are: a biological chassis (e.g. a strain of Escherichia coli), culture media, a DNA vector, a transcriptional promoter, a ribosome binding site, the open reading frame of the gene we wish to express, and finally, a transcriptional terminator region. Once we transform our bacterial culture, or more properly, our chassis, with this construction, it is possible (at least in theory) to produce the desired protein. But what happens when we want to express more than one protein and we make these proteins to interact with one another? We are then generating a more complex entity: a genetic system.
These systems present an in vivo behavior that can be quantified and modeled, since there are different mathematical formalism with which to represent genetic expression and regulation.
In conclusion, with standardization, it is possible then take for granted many technical procedures, so that one can focus on more abstract ideas, like the system’s function or the intended system’s behavior. This is known as “Abstraction Hierarchy”. In this way, a non-biology or non-bacteriology trained person can design his own biological system from the sole knowledge of the bioparts function. Moreover, it is possible to carry out experimentally an initial abstract mathematical model and, with the generated experimental data, to feedback the original model to increase its prediction power.