"artificial, engineerable, animal chloroplasts": coming soon to a laboratory near you!

ResearchBlogging.orgAs many of you are no doubt aware, both mitochondria and chloroplasts are thought to have come to us via microbial endosymbiosis (that is one cell living within another) with prokaryokes. Some photosynthetic bacteria eons ago found itself nestled inside another cell, realized it was a pretty sweet place to call home, and viola - a new cell organelle was born. OK fine, that is a bit of an oversimplification. The endosymbiotic theory is a bit more complicated, but that's the general idea. The details of how a symbiont over time could lose its unique identity and became a part of the host itself are keys that would unlock many evolutionary mysteries... mysteries that if we could understand them could allow us to better understand evolution, and possibly to engineer symbioses of interest.

I came across this article recently in a university-wide email newsletter. The article was a bite sized appetizer with hints of science fiction, green energy, history of life, not to mention a pretty picture with green sparkles. I needed more, so I found the paper where the study was formally written up.

I am a sucker for short, elegant, intriguing titles - ones that pull you in rather than make you re-read 3 times before you have any idea what the paper is about. "Towards a Synthetic Chloroplast" (open access: http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0018877) was just such a title. By the end of the abstract I was still engaged and wanting more.

Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices.

The paper made me think of one of my favorite books, "Oryx and Crake" by Margaret Atwood, which describes a world in which bioengineering has created a group of people with photosynthetic pigments in their skin. Hungry? No problem, just go sit in the sun for a while. So, what did these Harvard Medical School scientists do that seems to poise them somewhere along the path towards futuristic biological engineering?

First they injected individual Zebrafish embryos with up to 10 million Synechococcus elongatus cells before the embryos underwent their first cellular division. The researchers compared this to injections of E. coli (both living and dead) cells, and found that while both types of E. coli cells killed the developing embryos very rapidly, the S. elongatus cells seemed to have no impacts on the embryo's development. These embryos are clear, so light could penetrate to the photosynthetic bacteria injected into the cell. The bacteria were easy to track because of their red autofluoresence. Scientists saw the bacteria throughout the embryo (even in the brain and eye), but did not see any abnormal morphological changes in the embryos. The bacteria survived for 12 days within the embryos, and at that point the experiment was stopped because the fish began to become opaque, which would block the light that the bacteria would need to survive.

In a second experiment the scientists wanted to see if S. elongatus could invade mammalian cells if they were provided with the genetic machinery to do so. They identified genes in a different bacteria (invasin from Yersinia pestis Yersinia pseudotuberculosis (see comment below) and listeriolysin O from Listeria monocytogenes) that are known to cause invasion of mammalian cells. They then inserted these genes into S. elongatus. After this, 4.8% of the mammalian cells that they exposed these S. elongatus were positively fluoresent, showing that they had been successfully invaded by the engineered version of S. elongatus.

A third experiment involving macrophages showed that, unlike E. coli, the engineered S. elongatus was able to increase its fluoresence within the host cell (for a few days at least). This means that the bacteria were growing and dividing successfully within the cell.

The work described in this paper demonstrates, in a controlled laboratory setting, the first few steps that would be required to establish an intracellular symbiosis such as the one believed to have been responsible for the first chloroplasts (which therefore enabled the evolution of plants, an oxygen atmosphere, animals, and eventually you and I. There are no known mammalian endosymbioses, and work such as this is one way to understand why. The demonstration that it is possible to engineer a bacteria to be able to invade a mammalian cell has implications for synthetic biology in addition to allowing us insight into the evolutionary history of symbioses in general and even photosynthesis specifically.

Agapakis CM, Niederholtmeyer H, Noche RR, Lieberman TD, Megason SG, Way JC, & Silver PA (2011). Towards a synthetic chloroplast. PloS one, 6 (4) PMID: 21533097

P.S. (5/9/11) I just learned the first author of this paper also blogs here, and wrote her own post about this work. Check it out here!