In “On the Difficulty of Conjuring Up a Dryad,” Sylvia Plath writes,
But no hocus-pocus of green angels
Damasks with dazzle the threadbare eye;
My trouble, doctor, is: I see a tree,
And that damn scrupulous tree won’t practice wiles
To beguile sight:
E.g., by cant of light
Concoct a Daphne;
My tree stays tree.
Perhaps if Plath had witnessed the extraordinarily leaf-like appearance of the sea slug Elysia chlorotica, or the supernatural glow of green algae within salamander eggs, it would have been easier for her to imagine a tree, anthropomorphized.
The intracellular relationship between photosynthetic algae (zooxanthellae) and coral animals was first reported in the late 1800s (Rosenberg et al. 2007). Symbioses between photosynthetic algae living within salamander eggs (also discovered over 120 years ago) were long thought to be intercellular. Recently, Kerney (2011) discovered that this relationship, where the algae are thought to confer valuable oxygen to the developing embryo, is actually intracellular. The sea slug Elysia chlorotica harbors green algae after ingesting it as a food source. The algal plastids continue to photosynthesize within the sea slug, providing it with energy and carbon. Careful investigation of this fascinating relationship has revealed that genes from the algal plastid (psbO) are transferred horizontally to the sea slug nuclear genome where it is expressed. These are just a few instances exemplifying the evolutionary impacts such intimate symbiotic relationships can have on organisms and biodiversity in general. Indeed, ancient endosymbiotic events are thought to have resulted in all the eukaryotic diversity seen on our planet today (Keeling 2010).
In an effort to better understand the evolution of endosymbiosis, as well as to provide new tools for advancing synthetic biology, researchers at Harvard Medical School have successfully engineered photosynthetic cyanobacteria to invade and divide inside mammalian macrophages. In the first of a series of experiments, Agapakis et al. discovered that Zebrafish embryos injected with ~ 10 million cyanobacteria at the single cell stage survived up to twelve days intracellularly with no apparent effects on the embryo (compared with E. coli, which killed Zebrafish cells within two hours). A second investigation proved cyanobacteria genetically engineered with invasin and listeriolysin (genes needed for mammalian host cell invasion into the cell surface and cytoplasm, respectively) could effectively enter mammalian cells. Incredibly, a third test showed that engineered cyanobacteria taken up by mouse macrophages were able to survive and begin dividing, rather than being digested (Agapakis et al. 2011).
A 2005 Nature review written by Drew Endy of Stanford University underscores the importance of foundational synthetic biology to progress in bioengineering. Endy states, “for biologists, the ability to design and construct synthetic biological systems provides a direct and compelling method for testing our current understanding of natural biological systems.” The work of Agapakis et al. illustrates this idea. In considering research that has shown photosynthetic bacteria surviving inside mammalian cells, popular media or science fiction fans might conjure images of people simply basking in the sunlight a few times a day in lieu of making that weekly trip to the grocery store. If you are anything like me, the thought of a future that does not involve ingesting cheese is just dreadful. Rest easy, caseophiles. The authors are not implying such engineered relationships could serve in place of biological systems (i.e. photosynthetic skin!), at least not yet. However, they do a really nice job of putting their research into the context of creating a unique platform for bioengineering (that could potentially fill gaps in our knowledge of the complex evolutionary dynamics of endosymbiosis).
As Endy eloquently suggests, “it is possible that the designs of natural biological systems are not optimized by evolution for the purposes of human understanding and engineering… thankfully, these concerns are best evaluated by attempting to surmount them.” With that in mind, a number of questions that might be addressed by follow-up studies of this engineered system come to mind. What is the response of the host immune system? How is it similar or different to that of other innocuous associations, such as in algae and sea slugs or salamander eggs? Does gas exchange appear to be beneficial to Zebrafish embryos as it has been in salamander’s eggs? Is it possible that the cyanobacteria could ever survive to adapt (assuming that photosynthesis would not be possible at some level of the hosts’ development due to sunlight not penetrating multicellular structures)? And due to their benign nature in vertebrate cells, might the cyanobacteria make safe and effective gene delivery vehicles for therapeutic treatments or vaccines?
This post has been submitted for the NESCent (National Evolutionary Synthesis Center) research blogging competition. Winners receive a travel award to attend the ScienceOnline 2012 science communication conference at North Carolina State University.
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
Endy, D. (2005). Foundations for engineering biology Nature, 438 (7067), 449-453 DOI: 10.1038/nature04342
Keeling PJ (2010). The endosymbiotic origin, diversification and fate of plastids. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 365 (1541), 729-48 PMID: 20124341
Kerney R., Kim, E., Hangarter, R.P., Heiss, A.A., Bishop, C.D., & Hall, B.K. (2011). Intracellular invasion of green algae in a salamander host. PNAS 108: 6497–6502.
Plath, Sylvia. (1957). On the Difficulty of Conjuring Up a Dryad. Poetry 90: 235-236.
Rosenberg, E., Koren, O., Reshef, L., Efrony, R., & Zilber-Rosenberg, I. (2007). The role of microorganisms in coral health, disease and evolution Nature Reviews Microbiology, 5 (5), 355-362 DOI: 10.1038/nrmicro1635