Bio- Bricks: The Lego Of Synthetic Biology

Introduction

Bet every scientist once played lego and built whatever they imagined, be it robots, bridges, buildings or minifigures of their favourite Star Wars characters. But who would have thought that synthetic biology has some similarities with this! Did lego bricks instil something in your hidden child because it did for so many researchers working with synthetic biology.

Now, the lab is a creative workplace with customizable biobricks ready to produce synthetic biology products such as therapeutic drugs, enzymes, pharmaceuticals, food processing systems, biofuels and many more.

LONG LONG AGO….OKAY, NOT VERY LONG THOUGH

BioBricks parts were introduced and described by Tom Knight at MIT in 2003.

Since then, various research groups have utilized the BioBrick standard parts to engineer novel biological devices and systems from drug delivery systems to synthetic babies (yes, just like the RPG games’ character customisation! But, this lies in the grey zone of bioethics.)

What Exactly Are Bio-Bricks?

Like lego being the building blocks to create different working and static models, the bio-bricks are DNA sequences that can perform various desired biological functions and mechanisms with feedback mechanisms.

A BioBrick, in short, is a man-made elementary DNA sequence that codes for RNA or Protein and can be readily assembled to produce more complex biological systems.

Example of a circuit consisting of bio-bricks

These parts share a common interface and are designed to be composed and incorporated into living cells to construct new biological systems. Now researchers are working towards making new genes or combinations of genes, using the four letters — or nucleotides A’s, T’s, G’s, and C’s — that make up DNA and a trial and error method to determine the best working combination for the desired process to be engineered.

BIO BRICKS GOT SOME PRINCIPLES TO FOLLOW

The BioBrick parts are used by applying the engineering principles of abstraction and modularization.

I know, some fancy words right there, right? Let's make it simpler.

ABSTRACTION is an engineering principle that allows us to ignore unnecessary details and focus only on a particular level of organization. (YES YES, Just like abstract photography!)

In synthetic biology, we use an abstraction hierarchy to help us organize our projects.

First and foremost, since synthetic biology programs encompass living systems using DNA, we must begin by ensuring we have all of the physical DNA required to build our sensor.

This takes us to the first level of abstraction: ensuring the availability of DNA sequences.

Once we have all of the DNA, we no longer have to deal with individual DNA sequences.

We can give each functional unit of DNA a part name and arrange it in the hierarchy of importance and order, which is the second level of abstraction.

There are three levels to the hierarchy:

1. Parts: Pieces of DNA that form a functional unit (example: promoter, Ribosomal binding site.)
2. Device: Collection set of parts with a defined function. In simple terms, a set of BioBrick parts put together forms a device.
3. System: Combination of a set of devices that performs the desired function.

The third level of abstraction by combining parts into devices.

A device is composed of several parts connected in a meaningful way. When dealing with devices, we just have to know their inputs and outputs to know their overall behaviour.

The fourth level is the final compilation for the formation of the system.

MODULARISATION is the degree to which components of a system can be separated and recombined. In industrial design, modularity refers to the technique that allows building larger systems by combining smaller sub-systems. In biological sciences, the term is often used to design “functional blocks” in organisms simply.

Examples Of Bio-Bricks

Commonly used (and some essential) components in a genetic circuit

• Promoter: DNA sequence that initiates the transcriptional machinery (binding site of RNA polymerase, which is the enzyme that is responsible for carrying out transcription) and leads to the transcription of the downstream DNA sequence.
• Ribosome Binding Site (RBS): RNA sequence found in mRNA(messenger RNA) to which ribosomes can bind and initiate translation.
• Repressor: Protein that turns off the expression of one or more genes in a feedback loop. The repressor protein works by binding to the gene’s promoter region, thereby preventing messenger RNA production (mRNA).
• Green Fluorescent Protein (GFP): Protein that exhibits green fluorescence when exposed to the blue to ultraviolet range. Typically used as a reporter of expression.
• Enhancer: Regulatory DNA sequences, when attached with specific proteins called transcription factors, enhancing the transcription of genes.
• Terminator: DNA sequence that marks the end of transcription and stops RNA polymerase from going any further.

BIO-BRICKS ASSEMBLY

BioBrick parts can be incorporated into a circular plasmid (extrachromosomal self-replicating DNA loop) in which the functional part is flanked by universal and precisely defined upstream and downstream sequences, called prefix and suffix, respectively. It is important to note that the prefixes, suffixes and the plasmid are not BioBricks.

Let’s again imagine bio-bricks as legos. Each lego block has standard-sized protrusions on its surface and grooves below, which allows any two blocks to be put together with relative ease. Similarly, each BioBrick is constructed such that two compatible parts (with the same protrusions and grooves) can be readily assembled. This compatibility is governed by the assembly standards.

The most common type of assembly is -

Standard Assembly

This uses normal cloning techniques based on restriction enzymes (scissors cutting the DNA strand at specific locations), ligation (joining the gene of interest in the sites where restriction enzymes have cut the strand), transformation (genetic material transferred to the desired host) and purification.

E(EcoRI), X(XbaI), S(SpeI) and P(PstI) are restriction enzymes that cut at specific sites. Ligating the so-called ‘digested’ DNA fragments yields a new genetic circuit.

The Parts Registry

The parts registry is where the exchange of data and material takes place throughout the synthetic biology community.

The registry is open access, whereby anyone can submit a BioBrick part. Most of the BioBrick submission is from students participating in the annual iGEM competition hosted every summer. The Registry allows the exchange of data and materials online, allowing rapid re-use and modifications of parts by the participating community.

Conclusion

We now know the functioning and the mechanism of the basic units in synthetic biology and have a deeper understanding of how synthetic biology can be yielded for producing genetically engineered organisms, devising cancer treatments, enhancing biofuel production, and producing essential and life-saving compounds like human-compatible insulin from microbes.

Bio-bricks opens a very different perspective of synthetic biology- the one of controlling all the components at the very basic level and working out the ideal combination for overcoming various challenges in fields of medicine, pharmacy, agriculture and biological resource management.

References:

Catalog

Biobricks

Biobricks