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.

 

–end &&reference

[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

 

Time To Question Bio-Engineering [Question Mark]

I came across this bio-ethics video when I re-watch Craig Venter’s three speeches in TED. This thoughts-provoking video is also available on its official TED page  just in case you don’t have the access to YouTube.

The contents of the speaker mainly contains three parts:

  • Typical transgenic technology;
  • Computer Controls Brains;
  • Synthetic Life, or synthetic biology.

And I’ll briefly analyse them separately to calm down your potential fear after you’ve watched it.

Transgenic technology, safe

Public fears and concerns towards transgenic plant or animal have been there for years even though the scientific expects in China, at least, acclaimed that they are safe. The reason why people are afraid of transgenic technology and furthermore reject it is that public people don’t know it at all, or have limited understanding.

You must have read lots of articles explaining why transgenic technology is safe, or on the other hand, dangerous. And here I believe current products of transgenic technology in your daily life are safe and healthy, because most of them are protein product indeed. It is the exogenous genes are translocated and expressed in the host, but the outcome is protein according to the known central dogma, hence the protein cannot hybridize with your genome so that you will not be mutated to Rice-Man. No need to  panic.

GFP with its variants under UV

As far as the illuminating-man is concerned in the video, it’s somehow exaggerating. Most GFP (green fluorescent protein) can only been seen by naked eyes under UV (ultraviolet light), which means if you wish to see the man with transgenic GFP, the man must be exposed to the harmful UV light. Possible?  To be firefly? Still a long way to go.

Hybridization, unknown

Hybridization, on the other hand, is completely a mess though it shares similarities with transgenic technology. That’s why the speaker put the bio-illuminating animals with hybridization animals.

It’s a regular and normal to be upset by the Liger, Tiglon, etc, due to people are born to be afraid of what they are unfamiliar with, so are scientists. Scientists cannot be confident enough explain the mechanisms why the hybridized cells can grow to matured individual, let alone predict the potential risks if the hybridized pork were on market. It is really like the magical Chinese traditional medicine. They don’t know how the mixed  herbal medicine work, but they are pretty sure how to get them mixed to cure diseases. The same things applies to hybridization. What hybridization do is just make use of a characteristic of cell (or strictly nucleus) — omnipotency.

Computer “Brains”

This remote-control cyborg beetle came to this world few years ago. It strongly reminds me of a series of comics named Star Fleet (or X-Bomber).

I’ve to confess that I’ve limited understanding about the research, but apparently it is a huge step in neuroscience.

Synthetic Biology, Bright Future

“Synthetic Life”, “Synthetic Biology” more fit for hybridization, I suggest, if Liger still haunts you. Now what about synthetic biology? Is it more endangering? Let’s hear how the father of the first synthetic life said,

It’s true Synthia’s parent is computer, not organic life. However, another truth is that Craig Venter never create a new life, but copy a life.

 

Basically the video included all the bio-tech into bio-engineering, and provoked your antipathy to bio-tech. But, be calm down please. It’s time to question bio-engineering? Probably just some parts of bio-engineering.