Breakthrough "genetic circuits" bring us closer to synthetic human cells

Illustration for article titled Breakthrough genetic circuits bring us closer to synthetic human cells

We're one step closer to building artificial cells. Synthetic biologists have found a new way to assemble "genetic circuits," components that perform logical operations in living cells. This breakthrough could facilitate the development of artificial cells designed to solve problems in medicine, energy, and the environment.


This new technique, which was developed by Boston University biomedical engineers Ahmad S. Khalil and James J. Collins, could equip synthetic biologists with an entirely new set of genetic components for them to do their work — a development that could significantly increase the size and complexity of genetic circuits that can be built.

In other words, the potential diversity and sophistication of artificial life just got a whole lot bigger.


A report in Genetic Engineering & Biotechnology News tells us how it was done:

Illustration for article titled Breakthrough genetic circuits bring us closer to synthetic human cells

Recent advances in designing proteins that bind to DNA gave the researchers the boost they needed to start building a new library of transcription factors. In many transcription factors, the DNA-binding section consists of zinc finger proteins, which target different DNA sequences depending on their structure. The researchers based their new zinc finger designs on the structure of a naturally occurring zinc finger protein. "By modifying specific amino acids within that zinc finger, you can get them to bind with new target sequences," Dr. [Timothy] Lu says.

The researchers attached the new zinc fingers to existing activator segments, allowing them to create many combinations of varying strength and specificity. They also designed transcription factors that work together, so that a gene can only be turned on if the factors bind each other.

Such transcription factors should make it easier for synthetic biologists to design circuits to perform tasks such as sensing a cell's environmental conditions. The researchers built some simple circuits in yeast, but they plan to develop more complex circuits in future studies. "We didn't build a massive 10- or 15-transcription factor circuit, but that's something that we're definitely planning to do down the road," Dr. Lu says. "We want to see how far we can scale the type of circuits we can build out of this framework."

The researchers are also hoping to apply their new transcription factors to human cells.

The study was published in Cell and can be found here.

Top image agsandrew/ Inset image via Cell.


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Creating proteins is one thing - transcription factors are composed of a few dozen to a few hundred atoms in various molecular configurations. Constructing an RNA factor, however, multiplies that by a factor of 10, and constructing a DNA factor multiplies that by a factor of 100 for even the most simple strands. Building a completely synthetic cell requires that all molecular structures that we want in the cell be plotted and encoded into the various tools the cell will have. Then we'll have to create an environment where the cell can build itself, provide the initial energy, and pray that the artificial factors work as designed and build a cohesive, functional system. Do you know the level of trial and error that goes into natural evolution? For every cell that survives, thousands upon thousands fail when mutations/changes occur - and this is in a system where we're talking, at most, the change of perhaps one encoding sequence. In the beginning, it took millions upon millions of combinations of amino acids to form the first "life". Everything in the process had to be perfect for any chance for success - and even then, some simple life was built better than others.

We know what life *should* look like, and we're getting pretty good with nanoscale technology and manipulation. But to the point of creating a synthetic human cell? Doubtful within the next 150 years unless computational barriers are broken within the next 10. (We may be able to process the simulations necessary if we achieve stable, long duration quantum computing) Nanotech enhancement, cybernetics, specifically targeted gene enhancement? Yeah, I can see that happening. But a fully constructed artificial cell? That's going to take a while longer.