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Scientists Synthesize Memory Loop in Yeast Cells; First Artificial Gene-Based Device Accompanied By Predictive Mathematical Model
16 September 2007
Researchers at Harvard Medical School have successfully synthesized a DNA-based memory loop in yeast cells. These findings mark the first time that a gene-based device is accompanied by a predictive mathematical model, and represent a significant step forward in the emerging field of synthetic biology. A paper on the work is published in the current issue of the journal Genes and Development.
After constructing genes from random bits of DNA, researchers in the lab of Professor Pamela Silver, a faculty member in Harvard Medical School’s Department of Systems Biology, not only reconstructed the dynamics of memory, but also created a mathematical model that predicted how such a memory “device” might work.
Some see synthetic biology as a means to boost the production of biotech products, such as proteins for pharmaceutical uses; molecules for environmental clean-up; or optimized fuels for transportation. Others see it as a means to creating computer platforms that may bypass many of the onerous stages of clinical trials.
Synthetic biology is an incredibly exciting field, with more possibilities than many of us can imagine. While this proof-of-concept experiment is simply one step forward, we’ve established a foundational technology that just might set the standard of what we should expect in subsequent work.
—Pamela Silver
A team in Silver’s Harvard Medical School lab led by Caroline Ajo-Franklin, now at Lawrence Berkeley National Laboratory, and postdoctoral scientist David Drubin decided to demonstrate that not only could they construct circuits out of genetic material, but they could also develop mathematical models whose predictive abilities match those of any electrical engineering system.
The components of this memory loop were simple: two genes that coded for proteins called transcription factors. Transcription factors regulate gene activity.
The researchers placed two of these newly synthesized, transcription factor-coding genes into a yeast cell, and then exposed the cell to galactose. The first gene, which was designed to switch on when exposed to galactose, created a transcription factor that grabbed on to, and thus activated, the second gene. It was at this point that the feedback loop began.
The second gene also created a transcription factor. But this transcription factor swung back around and bound to that same gene from which it had originated, reactivating it. This caused the gene to once again create that very same transcription factor, which once again looped back and reactivated the gene.
The researchers then eliminated the galactose, causing the first synthetic gene, the one that had initiated this whole process, to shut off. Even with this gene gone, the feedback loop continued.
Essentially what happened is that the cell remembered that it had been exposed to galactose, and continued to pass this memory on to its descendents. So after many cell divisions, the feedback loop remained intact without galactose or any other sort of molecular trigger.
—Caroline Ajo-Franklin
Most important, the entire construction of the device was guided by the mathematical model that the researchers developed. For synthetic biology, this kind of specificity is crucial.
Think of how engineers build bridges. They design quantitative models to help them understand what sorts of pressure and weight the bridge can withstand, and then use these equations to improve the actual physical model. We really did the same thing. In fact, our mathematical model not only predicted exactly how our memory loop would work, but it informed how we synthesized the genes.
If we ever want to create biological black boxes, that is, gene-based circuits like this one that you can plug into a cell and have it perform a specified task, we need levels of mathematical precision as exact as the kind that go into creating computer chips.
—Pamela Silver
The researchers are now working to scale-up the memory device into a larger, more complex circuit, one that can, for example, respond to DNA damage in cells.
Resources:
Caroline M. Ajo-Franklin, David A. Drubin, Julian A. Eskin, Elaine P.S. Gee, Dirk Landgraf, Ira Phillips, and Pamela A. Silver. “Rational design of memory in eukaryotic cells” Genes & Dev. 21 (18)
David A. Drubin, Jeffrey C. Way and Pamela A. Silver. “Designing Biological Systems” Genes & Dev. 21 (3):242-254, 2007 (Open Access)
September 16, 2007 in Synthetic Biology | Permalink | Comments (5) | TrackBack (0)
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Comments
All of this had been seen before in nature, and the design of which has been made in theory, proving it like this a small step, that will be forgotten in the more significant steps to come.
Posted by: Ben | Sep 16, 2007 1:59:18 PM
My genious is unherralded.
Posted by: Ben | Sep 16, 2007 5:29:09 PM
Looks like the spoofer's back.
Posted by: Neil | Sep 16, 2007 9:45:57 PM
Fascinating, but what is the link to green cars?
Posted by: Rafael Seidl | Sep 17, 2007 4:42:06 AM
Rafael: "Fascinating, but what is the link to green cars?"
Bacteria adapting to different kinds of input food. So, one bacterium for cellulose, cane, or corn sugar, for example. The bacteria will "know" what kind of genes to fire off depending on the input foodsource.
Posted by: km519 | Sep 17, 2007 5:55:47 AM
