Genetic Circuits – Hope for Better Cancer Therapy?
With the beginning of the twentieth century, the world saw the first electronic circuits that endeavoured to revolutionize technology and medicine alike by the end of the century. A hundred years down the road of time, biological engineers at Mass Institute of Technology (MIT), United States, have managed to design genetic circuits using genes as substitutes for transistors and capacitors.
Synthetic biologists designed cellular circuits by using genes as interchangeable parts. These circuits can perform functions like sensing environmental conditions. However, synthetic biologists are still working with a small handful of genetic parts already known. They managed to design all the aforementioned circuits by rearranging the same circuits repeatedly.
The major hindrance to expansion of possible circuits is that genes interfere with one another. In electronic circuits on a silicon chip, all the components are isolated from each other. However this is not possible in cellular circuits because all the cellular machinery for reading genes and protein synthesis is jumbled together. It’s imperative to cross-check and consider whether the proteins controlling one part of the circuit could interfere with another just as drugs need to be checked for side effects and contraindications on the macroscopic systemic level.
In biological circuits the inputs and outputs are proteins like activators or chaperones that control the next circuit. The researchers used the approach of ‘directed evolution’ to reduce cross-talk between circuit components. It’s a trial and error process similar to that used for creating recombinant genes. The process requires mutating a gene to create thousands of similar variants that are tested later for the desired trait. The best candidates are chosen and screened again until the optimal gene is created.
Christopher Voigt, an associate professor of biological engineering at MIT and his students have taken a different approach towards cellular circuits in order to avoid the bottleneck of gene interference. They developed individual circuit components that would not interfere with each other and then stitched them together. They have managed to produce the most complex synthetic circuit ever built that can be used in cells to precisely monitor their environment and initiate an appropriate response accordingly.
To build larger circuits using hundreds of smaller circuits in different combinations, computer programs are required that Voigt’s team has already begun working on. Simultaneously they’re applying the knowledge of promoters and chaperones to create a sensor for an industrial yeast fermenter. This sensor will allow the yeast to monitor their own environment and adjust their output accordingly. Previously they succeeded in designing bacteria that could respond to light, capture photographic images and those that could detect low oxygen levels and high cell density. The latter two could be used for detection of tumours as both oxygen deficit and cell density are found in these conditions.
Developments like these in the arena of medical physics give us new hope for detection and treatment of cancer in its early stages through gene therapy, perhaps even without long term invasive and radiological procedures and hence a relief from the stigmatizing side effects of treatment.
Source: MIT News Office.
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