Synthetic Biology: Hacking the Genome (1/2)

Biological systems, customized.

Resurrecting long-extinct species. Cooking up whole living organisms from scratch in a lab. Replacing traditional industrial manufacturing processes with cleaner, more efficient biological ones.

Sounds like a bunch of wacky science fiction, I know, but this is all very, very real — and it’s a field called synthetic biology.

Synthetic biology is the study of how we can leverage interesting engineering tools and processes to get to not only a better understanding of how DNA works, but also to create a faster, more efficient way to chemically synthesize a genome from a set of catalogued DNA sequences.

This includes:

  1. Standardized biological parts
  2. Computational protein design
  3. Natural product synthesis
  4. Synthetic genomics
(P.S. Natural product synthesis and synthetic genomics will be covered in part 2 of this series, so keep your eyes peeled for updates!)
Image result for synthetic biology
Source: ThermoFisher

Genome mass-production

Seems like anything humans can get their hands on, we want to mass produce. Food, clothing, plastic toys… and now genomes. For a couple years now, researchers have been creating a comprehensive catalogue of standardized gene sequences that fulfill specific roles. Think of this as pieces of Lego that perform different functions; one piece is a rotating plate, the other is a large flat plane that acts as a building base, and another one is a triangular piece. In the same way, having standardized biological parts means you’ve got a database of mix-and-match genetic parts to make your own custom blueprint of life.

This makes it a lot more accessible for genetic researchers who are looking to modify their test organisms in a very specific way. For example, if you wanted your bacteria to become glow-in-the-dark, you could just pop into MIT’s Registry of Standard Biological Parts to get that secret sauce you needed. (Well, it’s not really that easy, but you get the point.)

Source: SD Times

There wouldn’t be any risks in terms of the reliability of these pieces, either – all of the Registry’s stored sequences have been standardized using the Biobrick standard. This means that even if developers work on building these sequences independently, the end result will still be compatible with any other project that complies with Biobrick.

What’s the implication? Well, with access to this kind of Registry, scientists will have to spend much less time piecing together genomes and more time actually experimenting with them. You see, it turns out that no one actually really knows how DNA works just yet – sure, we can associate basic functions to certain sequences, but we don’t quite understand the long-term implications of these kinds of modifications (simply because the field hasn’t been around for a very long time). Having access to these standardized biological parts will help advance our understanding of the human genome much faster, so we’ll be able to more accurately assess these risks.

Computing Living Organisms

If DNA is the blueprint of life, proteins are the tools that actually build life. They help us breathe, move our muscles, feel happy or sad, and are pretty much at the bottom level of any living function you can imagine. We can assume, then, that the fastest route to artificially engineer organisms to become better, faster, stronger, sometimes prettier, would be to tinker with these proteins.

Up until recently, researchers would come up with new proteins by messing around with preexisting ones or scouring nature to find proteins that haven’t been discovered yet. Coming up with new proteins that weren’t just useless 3D scribbles was pretty much impossible — the computing power people had access to back then just couldn’t handle the sheer complexity of these tiny things.

No, seriously, how could something so microscopic be so mind-blowingly complex? Just one amino acid is already around 20 atoms. String them up, and you get a polypeptide chain. Then you slap multiple polypeptides together to finally get a protein. Not to mention all the funky folding and twisting that goes on (which is a structural aspect that’s a lot more important than I’m making it sound — the most important part, actually). For example, take a look at this guy here:

Source: Graphs of Protein Structures

At first sight, it looks a lot like a garbled mess of yarn, but in reality even a single change in the way one of these polypeptide chains are twisted will have a huge impact on the function of the protein. Because this has always been too much for computers to handle, we were never really able to properly build our own proteins. But now, we finally have the computing power to actually simulate these hugely complex structures and even design them from scratch (called de novo design), and the results can have enormous potential.

For example, by building new enzymes (which are a type of protein) we can accelerate and optimize vital biological processes. Enzymes are catalyzers of reactions; they make them a lot faster without being expended during the reaction. Therefore, by making these more efficient we can rig the whole organism to function at a much higher level.

Protein design can also help towards curing major diseases like Alzheimers’ that involve protein to protein interactions. By building proteins that have a specific affinity to one of these proteins, you can effectively block this reaction from happening at all.

Two Sides

Synthetic biology is the field of the future. It has progressed exponentially ever since the beginning of the Human Genome Project and the discovery of CRISPR-Cas9 gene editing, and will continue to grow until we’ll be able to not only eradicate every single genetic disease known to man, but also optimize and finely engineer the human body to the very limits of evolution.

On the other hand, it also opens up opportunities to biological warfare (imagine… weapons of mass destruction that are engineered to target individuals with a specific set of genes), and huge ethical concerns. As with any innovation, there’s a push and a pull — but one thing is for sure; synthetic biology is changing the world a lot faster than people realize, and it’s high time to inform ourselves.

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