To understand how a cell works, you have to take it apart and put it back together. That's the thinking behind synthetic biology.
We now know how to identify genes, segments of DNA that code for proteins, and how to get copies of these genes to replicate in different organisms. For example, we can introduce a human gene encoding an antibody into a plant and we can even get a protein found in spider web silk to be expressed in the milk of cows.
The ultimate dream of a synthetic biologist is to take different cloned genes, wrap them in a cellular membrane, and provide the basic elements for RNA and protein synthesis to create a self-replicating cell that’s never existed before.
Why Make a Synthetic Cell?
If we can already make transgenic animals and plants, why make a synthetic cell? Synthetic biologists believe that because synthetic cells will be precisely engineered to contain known genes that interact in known ways, the cells will behave in a more predictable fashion.
Some other reasons:
- If you can build a cell from scratch, you can understand how it works.
- Synthetic cells may be used to produce chemicals without relying on harmful solvents or toxic processes; i.e., synthetic biology could lead to “green chemistry.”
- Synthetic cells may be used to create alternative sources of energy.
- Synthetic cells may be designed to produce large quantities of proteins to treat diseases.
- Cells may be engineered to attack environmental contaminants, aiding in bioremediation efforts.
Despite the logic of this and the basic tools of DNA cloning already in hand, synthetic biology is still in its infancy. Putting together the over one hundred genes it can take to create an artificial cell is not a trivial task!
Creating a Biological Circuit
Recently, scientists at Harvard Medical School, led by Dr. Pamela Silver, in conjunction with researchers at MIT, took an exciting step forward in this field.
The scientists placed two genes, each coding a transcription factor (TF), into yeast cells. Transcription factors are proteins that regulate the expression of messenger RNAs. The code of a messenger RNA is read by the cellular machinery involved in protein synthesis (e.g., transfer RNAs and ribosomes), allowing for the assembly of amino acids into a protein product.
The first TF gene was engineered to respond to galactose, a kind of sugar molecule, by producing a TF protein (TF1) that could bind to a second TF gene, which in turn would produce a second TF protein (TF2). The TF2 protein could also bind to the second TF gene to increase its own expression. In other words, the scientists created a molecular circuit with a positive feedback loop.
When engineered yeast cells were exposed to galactose, the first gene switched on and the cells produced the TF1 protein. Expression of the TF1 protein caused the second TF gene to turn on and the TF2 protein was expressed. The TF2 protein bound to the second gene, as expected, causing the cells to make more TF2 protein. The scientists then took the galactose away and the first gene turned off. However, the second gene continued to express the TF2 protein. Although the yeast cells were no longer exposed to galactose, the cells had a molecular memory of their exposure because they continued to express TF2. Interestingly, the yeast cells passed on this memory to their descendants as they divided and produced more cells that had never been exposed to galactose.
Although the engineered yeast cells were not completely artificial cells, this study demonstrates that it’s possible to design a transcription-based logic device. Precise control over the switches that turn genes on or off in a cell can allow us to control how cells react to environmental cues as well as to artificial stimuli. This lets us control the behavior of cells and create new biological tools.
For more information about this study, see Ajo-Franklin, et al. Genes and Development, Volume 21, Issue 18: September 15, 2007.
