This is almost becoming customary, being late with new posts and all. This post is actually around a month old but trust me, it’s a good’un. Sorry, once again.
So, we can hack cells? Yes, yes we can. Well, we could before but now it is simpler.
Our (humans, obviously) bodies are comprised of trillions of cells, computers at a molecular level that adjust and react to the signals they receive from both each other and the environment in order to carry out intricate processes. Synthetic biologists engineer living cells, controlling how they behave by converting genes into programmable circuits. This process has now been made easier thanks to a new, simplified platform outlined by Dr Wilson Wong (Assistant Professor (BME), Boston University) in which mammalian cells can be targeted and programmed as genetic circuits, more efficiently and quickly.
“The problem synthetic biologists are trying to solve is how we ask cells to make decisions and try to design a strategy to make the decision we want it to,” Wong stated. He also added that he and his team approached their design of these new circuits very differently, creating “a framework for researchers to target specific cell types and make them perform different types of computations, which will be useful for developing new methods for tissue engineering, stem cell research and diagnostic applications, just to name a few.”
Circuit design in electronics has historically been the inspiration for engineered genetic circuits, following a similar suit by utilising transcription factors (proteins that actuate DNA to RNA conversion). However, this is demanding to work with as it is incredibly difficult to predict a completely new strand of genetic code. Mammalian cells are even more unmanageable, due to their highly variable environment and complex behaviours, resulting in the electronics approach as something that is lacking.
DNA recombinases are Wong’s approach. Enzymes that cut and paste, #word, small parts of DNA sequences to allow for a more specific manipulation of cells and their behaviour. The resulting platform has been named “BLADE,” an abbreviation for “Boolean Logic and Arithmetic through DNA Excision,” yeeeeah. It refers to the computer language that the cells are programmed with and the computations they can be programmed to carry out, Boolean being a data type with two values to represent the truth values of logic and Boolean algebra, something the computer scientists know about and a discussion for another time, perhaps. The bottom line is, BLADE will allow researchers to use different signals in one streamlined device to control the behaviours of targeted cells.
Benjamin Weinberg, a graduate student in Dr Wong’s lab, stated that the idea for the new platform was to “build a system simple and flexible enough that it can be customised in the field to get any desired outcome using one simple design, instead of having to rebuild and retry a new design every time.” With BLADE, it is possible to implement any combination of computations that synthetic biologists may want in mammalian cells. Weinberg added that although, for this particular paper, the team may not have built the particular behaviour desired but they illustrated that with BLADE it is possible to “build the circuit you need to fulfil the behaviour you are looking for.”
The paper, published in Nature Biotechnology, showcases over one hundred examples of circuits built using the BLADE platform. Researchers intentionally built complex circuits with very complicated functions to show the possibilities of the system’s design, with some that even programmed human cells to add or subtract numbers. Before BLADE, any of these circuits would’ve taken years to build and function, as well as lots of trial-and-error to make them work in the way planned. After carrying out synthetic biology research for 15 years, Wong has said he’s “never seen such complex circuits work on the first like with this platform.”
“We’re excited to get it out there so people can start using it, and we’re excited to see what they come up with,” said Wong.
I, for one, agree.