Synthetic Biology in Mammalian cells

Last post I mentioned an interesting research introducing RNA interfere system in bacterium and archaea. It gives a new sight into how similarities the three kingdoms share, and potentially what have been done in mammalian cells can be applied into E.coli to enrich the toolbox of synthetic biologists.

Today let’s take a glimpse at what is on earth the progress in mammalian synthetic biology world. Is the bio-system as feasible to engineer as E.coli, just like iGEM? Is the field quite matured enough? Or still long way to go?

As usual, I chase a line and here share out the reviews that probably gives me the answer.

  1. Weber, W., & Fussenegger, M. (2009). Engineering of synthetic mammalian gene networks. Chemistry & biology, 16(3), 287-97. Elsevier Ltd. doi:10.1016/j.chembiol.2009.02.005
  2. Weber, W., & Fussenegger, M. (2010). Synthetic gene networks in mammalian cells. Current opinion in biotechnology, 21(5), 690-6. Elsevier Ltd. doi:10.1016/j.copbio.2010.07.006
  3. Greber, D., & Fussenegger, M. (2010). An engineered mammalian band-pass network. Nucleic acids research, 38(18), e174. doi:10.1093/nar/gkq671
  4. Weber, W., & Fussenegger, M. (2011). Molecular diversity–the toolbox for synthetic gene switches and networks. Current opinion in chemical biology, 15(3), 414-20. Elsevier Ltd. doi:10.1016/j.cbpa.2011.03.003
  5. Weber, W., & Fussenegger, M. (2011). Emerging biomedical applications of synthetic biology. Nature Reviews Genetics, 13(1), 21-35. Nature Publishing Group. doi:10.1038/nrg3094
  6. Karlsson, M., Weber, W., & Fussenegger, M. (2012). Design and construction of synthetic gene networks in mammalian cells. Methods in molecular biology (Clifton, N.J.), 813, 359-76. Humana Press. doi:10.1007/978-1-61779-412-4_22

Based on the above researches, things in mammalian cells are not splendid engineered as E.coli, probably due to our limited understanding towards eukaryotes.

Nevertheless, there still are some sparkling researches. Here I raise one for example — Rapid Eraser, or precisely, Auxin-controlled protein depletion device.

Though it’s an old story, the bio-eraser inspires a lot. Another real old story is bio-film, the noted first E.coli photograph. An awkward problem  is the E.coli bio-films are ONCE-only. If you need another photo, you need buy one more new film .  Any modification? Protein Depletion!

Furthermore, let me explain why protein depletion device is wonderful first. Since it’s easy to enable E.coli express different color with natural dye seen under naked eye (seen E.chromi), or with GFP/RFP under UV light, what about rainbow sparkling E.coli Biofilm? The biofilm is more like a neon light. The E.coli itself can change its color from red to yellow, to green, and back to red periodically.

E.chromi

It’s Rainbow E.coli !!!

So how the protein depletion device works? Degron !!! A degron is a specific sequence of amino acids in a protein that directs the starting place of degradation. Once activated by ubiquitylation, for example, the protein will be rapidly degraded, thus seems to be erased.

As for auxin, auxin is employed as the inducing signal. As auxin-triggered degron system is conserved in yeast, avian and mammalian cells, it can be applied to yeast cells, and will not interfere with other proteins as signal noise or lead to fatal error.

What ‘s the speed? 97% depletion in 15~30min ! Very satisfying.

It is recommended that you read the paper [1] for further details.

 

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[1] Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T., & Kanemaki, M. (2009). An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nature methods, 6(12), 917-22. Nature Publishing Group. doi:10.1038/nmeth.1401

 

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