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Paper Review #2
"Synthetic Gene Networks that Count"
Friedland, et al., 2009
The field of synthetic biology uses engineering principles to analyze genomic circuits, in order to then build small biological devices. As biological circuits take a complex system and turn it into a simple version, such devices can allow for a better understanding of the processes behind biological circuits that evolved naturally. It is important to remember, however, that these simple versions do not accurately represent the biological system itself; they are models.
Complex circuits maintain their own distinctive properties. In the future, as circuits are built with higher and higher complexities, we will gain a deeper and deeper understanding of cells and organisms, and the interactions within them.
Synthetic gene circuits can be built based on digital circuits and devices, allowing for the capacity to program, engineer, and design cells using basic principles of modern computing. One such principle is counting.
For bio-engineers and molecular biologists, such devices facilitate the programming of new, specific cellular behaviors and the creation of therapeutic agents, both with broad implications in terms of medical care.
A counter is a vital component in digital circuits and computing. It maintains memory of events of objects, representing each number of objects as a different state.
Cells many times need precise counting of strictly regulated processes or biomolecules in order to keep metabolism and growth at the ideal levels.
Mechanisms of counting have previously been reported in telomere length regulation as well as cell aggregation.
These system behaviors seem to be based upon a thresholding effect, meaning a certain critical molecule number or density has to be reached in order to see the phenotype change.
A counter for cells would have broad implications in terms of complex synthetic programming and a variety of biotechnological applications.
Friedland, et al., engineered two complementary synthetic genetic counters in E. coli with the capacity to count up to three induction events.
They developed the first counter, a Riboregulated Transcriptional Cascade Counter, based on a transcriptional cascade with additional translation regulation (RTC 2-Counter and RTC 3-Counter).
Their second counter design was based on a recombinase-based cascade of memory units. It was termed the DNA Invertase Cascade (DIC) Counter, and was created by chaining together modular DNA-based counting units (single-inducer DIC 2-Counter and single-inducer 3-Counter).
They measured fluorescence of Green Fluorescence Protein (GFP), thereby measuring transcription of the downstream gene, through flow cytometry.
These modular devices make it possible to count assorted user-defined inputs over a range of frequencies. They can be further broadened to count higher numbers as well.
Friedland AE, Lu TK, Wang X, Shi D, Church G, and Collins JJ. Synthetic Gene Networks that Count. Science [Internet]. 2009 May 29 [cited 2011 April 20];324(5931): 1199-1202. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690711/
*Note: All citable information was taken from this original paper.
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