Team:BostonU
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2016
Synthetic biologists seek to control the behaviors, specifically those behaviors dictated by gene expression. To do this, they look to cells to provide a blueprint for their designs. However, scientists like Timothy Lu have noticed a distinct dichotomy in the field of synthetic biology surrounding cellular blue prints,
“Living cells implement ... both analogue- and digital-like processing ... In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately.”
Currently in the field, most methods of gene regulation are either digital (transcriptional activators, repressors, and inducible circuits) or they are analog (oscillatory circuits). This summer our team desires to develop a synthetic promoter toolkit that can generate both digital and analog genetic expression.
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Synthetic biologists seek to control the behaviors, specifically those behaviors dictated by gene expression. To do this, they look to cells to provide a blueprint for their designs. However, scientists like Timothy Lu have noticed a distinct dichotomy in the field of synthetic biology surrounding cellular blue prints, “Living cells implement ... both analogue- and digital-like processing ... In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately.” Currently in the field, most methods of gene regulation are either digital (transcriptional activators, repressors, and inducible circuits) or they are analog (oscillatory circuits). This summer our team desires to develop a synthetic promoter toolkit that can generate both digital and analog genetic expression. To do this, we have developed three main aims for our work this summer. The first aim is to develop a digital toolkit that is tunable, modular, and orthogonal. Tunable refers to a system with consistent replicable levels of gene expression similar across several activating complexes. Modular refers to a tolerance to several genes of interest and genetic architectures. Orthogonality refers a system that will not activate endogenous genes as well as produce cross talk over several activating complexes. The second aim is to develop the analog component of the toolkit by developing a grade genetic expression. By this, we are referring to a system that can produce low, medium, and high levels of gene expression with the same level of accuracy as the digital component of the toolkit. Finally, our system must be able to function in the complex cellular environment of human cells to prepare it for ultimate use in therapies. To perform these task, we discussed the various methods by with gene expression can be modulated in cells. These techniques include Zinc Finger, TALEN, and CRISPR/dCas9. The decision was reached that CRISPR/dCas9 would be the tool of choice for our toolkit due to both its ease to engineer as well as its legacy in the foundational research category of iGEM (see Freiburg 2013). As a foundational advancement focused group, applications for our project are years off, however there are several speculative areas of interest. In many cases production of proteins harmful to host cells, like antibiotics, are difficult to do in large quantities due to the risk of death to host cells. By introducing a scalable response, scientists can increase efficiency without killing the host cell by properly finding the point at which the cells metabolism can no longer contend with the stress. In regards to therapeutics, this system could either allow doctors to properly dose a patient with gene expression in a similar way to how traditional pharmaceuticals functions. In addition, if this system was integrated with genetic logic circuits, the level of gene expression during a therapy could be theoretically modulated after implantation to once again better address the needs of a patient.
