Team:USP-Brazil/Applications

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Applications

Quorum sensing systems can be an innovative tool, enabling the design of a complex system with a cascade of controlled reactions. A good use of this will enhance the success of systems that utilize bacteria as biofactories. One straightforward and already implemented application would be of coordinating single cell genetic behaviour based on the population's overall state, which means robustness of behaviour along the population, a much needed factor for other applications. Other applications, though, have their success impeded by the amount of crosstalk in quorum sensing systems.

Such is the case for synthetic communities, where you can design division of tasks between strains of bacteria, whose population growth could be mediated by quorum sensing. The strengths of two very different strains could be harnessed at the same time, while avoiding metabolic burden and complicated molecular biology tests and procedures to try and force E.coli to produce something unnatural to it. Quorum sensing also brings interesting possibilities to the concept of biological logic gates.

Not only we can use molecular biology's "chemical wires" to connect and bring life to genetic circuits, but in some way quorum sensing gives us the possibility of "chemical telecommunication", when transmitting a signal from on bacteria to others at some distance apart. Logic gates could have, then, an extra layer of complexity, by differentiating the position and quorum sensing neighborhood of a bacteria. As coordinated population behaviour, there could also be a system that uses quorum sensing as a modulator to a kill switch, which keeps the population in a default threshold or outright kills all the population depending on some external input.

One possibility that came to our minds when studying quorum sensing was the idea of using incoherent feed-forward loops (IFFLs) to diminish crosstalk between pathways. The way this loops work is by an element of a circuit having a negative indirect effect (repression) over something which already suffers a positive effect (activation) by the first element. This way, the effects could cancel out and negate the effect of the first element to the second.

At first this may seem paradoxical, but it could be exactly the right thing if you want to make two elements independent of each other by eliminating unwanted interaction. Quorum sensing suffers from this, with crosstalk as a very unwanted interaction. We hypothesized such a circuit, and came to the conclusion that a double-repression system would be needed, to counteract the repressor hindering the other system's native expression instead of just the crosstalk.

All of these examples are only a snippet of all the applications for this incredible mechanism. With more understanding it's secure to say that several areas of the society will benefit from works with quorum sensing!

References

  • Chan, Clement TY, et al. "'Deadman'and'Passcode'microbial kill switches for bacterial containment." Nature chemical biology 12.2 (2016): 82.
  • Brophy, Jennifer AN, and Christopher A. Voigt. "Principles of genetic circuit design." Nature methods 11.5 (2014): 508.
  • Nathan I Johns, Tomasz Blazejewski, Antonio LC Gomes, Harris H Wang, “Principles for designing synthetic microbial communities”, Current Opinion in Microbiology, Volume 31(2016), Pages 146-153, ISSN 1369-5274, https://doi.org/10.1016/j.mib.2016.03.010.
  • D.R.Michele, M.R.Yue, H.K.Ann. “Can the Natural Diversity of Quorum-Sensing Advance Synthetic Biology?” Frontiers in Bioengineering and Biotechnology, volume 3 (2015), 2296-4185, doi: 10.3389/fbioe.2015.00030
  • R.J.Case, M.Labbate, S.Kjelleberg. “AHL-driven quorum-sensing circuits: their frequency and function among the Proteobacteria” The ISME Journal, volume 2, pages 345–349 (2008)
  • M.E.Taga, B.L.Bassler. “Chemical communication among bacteria” Proceedings of the National Academy of Sciences, Nov 2003, 100 (suppl 2) 14549-14554; doi:10.1073/pnas.1934514100