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Engineering with DNA

Photo by: Martina Ikonen

Genetic Engineering
Genetic engineering is like programming. You design code that defines what your computer is doing and how it reacts to different inputs. But in this case, the code is DNA, the computer is the cell and the inputs could be molecules or light. You deploy your code by giving your cells high voltage shocks or infect it with a virus. Don’t try this with your computer!

Working with cells and DNA looks actually quite hilarious. We have a big number of small, transparent 1-2 ml plastic tubes and then we move transparent liquids from one tube to another. And then we shake, spin, heat or freeze them. In the end of the day, we pour them on a plastic plate with some gel and hope next morning there will be spots or colonies on it. That’s pretty much how every-day work in the lab looks like. While it may seem like nothing happens, there’s a lot going on! There’s just no way of seeing it.

Pink bacterial colonies on a plate (Photo by Minnamari Salmela)

Cut, Copy and Paste DNA
As you know, DNA is the blueprint for cells. It is a huge molecule but it’s still so small that even the best electron microscopes only capture a faint shadow of it. But we don’t have to see the DNA to be able to work with it. Usually, the basic working template is a plasmid. It’s a circular DNA molecule of a few thousand bases (= letters, remember those A, C, T and G). We’ve got some very neat tools to edit these plasmids. For example, we can copy and paste sequences (and I’m sure you agree copy-paste is a very, very useful feature).

Then we’ve got a scissor tool called a restriction enzyme. It cuts the DNA at a sequence that is specific to every enzyme. For example, the EcoRI enzyme cuts the DNA at GAATTC site. Then we have another tool called ligase which can glue the cut ends back together. With these tools you can cut DNA from one origin, combine it with another piece of DNA and paste it to a new plasmid.

Then there’s a PCR (polymerase chain reaction) machine. Don’t let the name fool you, it’s really just block of metal that can change its temperature very quickly! You can use this machine to copy your DNA (see link) and replicate huge numbers of it to the extent that it’s visible by eye.

Synthetic Biology -the Next Level of Bioengineering
Using these terms in life science is a huge mess! There is bioengineering, biotechnology, biomedical engineering, bioprocess technology, systems biology, genetic engineering and now there’s this synthetic biology, which is the new guy in the gang. And even that has many definitions and disagreement. Here, it’s about designing cellular functions, building on top of what the cell already is. But people haven’t really figured out how to call this stuff, as we are talking about a rather young field of science and engineering.

Synthetic biology is all about engineering, sharing and simplifying. It splits DNA into modular parts, each with distinct roles or mechanisms. These parts can be combined with each other to build more complex systems, just like Lego bricks (and therefore we call these parts BioBricks). You don’t need to know how Legos are made or what kind of material they are made of as long as they work as you expect. Same goes with BioBricks, although deeper knowledge brings greater opportunities.

Let’s use an example to go through the whole process. You notice that your feet smell awful and you would like to design bacteria that would smell like flowers when your feet get sweaty. First, you isolate the bacteria from your feet. Then you design a system that can sense the sweat and trigger the flower scent production:

Diagram for a synthetic gene circuit producing flower scent when “Sweat” is present (by Oskari Vinko)

In the picture above, there’s a diagram of the parts needed in the system. Promoters are essential pieces of DNA that tell the cell which regions should be read. The terminator, in turn, tells when to stop reading. In between, we put the gene of interest, which is now the recipe for a sweat sensing protein (SSP). We also need an RBS (Ribosomal Binding Site, more info here). The SSP should become activated only when “sweat molecule” is bound to it. The active SSP then binds to the promoter and activates the production of the heavenly flowery smell.

It’s All about Sharing
BioBrick Foundation has a huge collection of different DNA parts and you can download any of them at their website. You can browse different categories or search a specific part you’ve got in mind. In addition to the sequence, each part also has a description and a page for experiences by other users. This way, you can check how the part worked for other people and what kind of results they had.

When you design a new part, like the sweat sensor protein in our example, you can send it to BioBrick registry so that others can use it. It is very important to properly describe the properties of the part so that people can find out if that’s the part they need. Synthetic biology relies on the sharing community and proper description of the DNA parts. In principle, synthetic biology doesn’t mean anything new compared to traditional biotechnology. As an analogy, text documents, pictures and videos have been there for a long time. Internet is nothing else than these parts linked together and shared with the world. And as you know, this makes a huge difference! And so will synthetic biology, I believe.

If you would like to try to build something on your own or in the classroom, check out DNA Tinker Studio. They are going to make starter kits so that you can build something on your own.

Oskari Vinko originally studied physics and mathematics at Aalto University. He jumped into molecular biosciences at University of Helsinki and is now doing a Master’s degree in synthetic biology in cybergenetics group at ETH Zürich, Switzerland.