Molecular manipulation of algae
July 30, 2012 § Leave a comment
Until I sat down to write this post, I didn’t have a proper appreciation of algae. These organisms are used to make products such as edible seaweed (sushi, anyone?), fertilizers, the dairy additive carrageenan (a vegan alternative to gelatin), and the agar on which molecular biologists and biochemists grow their bacteria. Researchers are tinkering with algae to expand the portfolio of products to include biofuels, synthetic biology building blocks, recombinant proteins and antibodies.
But the proper exploitation of algae relies on being able to fully manipulate their molecular biology and biochemistry. Getting imaging agents and drugs, for example, past the double barrier of the algal cell wall and plasma membrane remains a difficult problem. In short, researchers don’t have the appropriate molecular tools. But in a paper just out in the Proceedings of the National Academy of Sciences, researchers describe special transporters that can carry molecular cargo past the algal cell wall and plasma membrane.
The team led by Bahram Parvin at the Lawrence Berkeley National Laboratory and Paul Wender of Stanford University adapted guanidinium-rich molecular transporters so that they could get past the double barrier of the algal cell wall and plasma membrane. These transporters originally were developed by Wender’s group to get across the plasma membrane of mammalian cells.
When developing the transporters more than a decade ago, Wender says, they used nature as inspiration. Natural proteins use arginine-rich sequences to cross barriers. So Wender’s group reverse-engineered the Tat protein so that the peptide would have four to 20 residues each of arginine and guanidine. This reverse-engineered peptide was able to ferry cargo across the mammalian cell membrane.
In this latest piece of work, Wender, Parvin, LBNL’ s Joel Hyman and Stanford’s Erika Geihe and Brian Trantow demonstrated that the same kind of reverse-engineered peptide can cross more formidable barriers, like the double barrier in algae. Using Chlamydomonas reinhardtii and other algal species, the investigators showed that the transporters successfully carried across small-molecule probes, like the optical agent fluorescein, and protein complexes like strepavidin-biotin. Hyman says the fact that the investigators were able to get fluorescently labeled agents like fluorescein into algae may pave the way to getting radioactively tagged molecules into algae for applications involving radiochemistry.
Wender says the approach is the first of its kind to get molecules inside algal cells. With the method, he says, “We can now ‘communicate with,’ study and manipulate algae and thereby learn more about their fundamental biochemistry and how we might be able to use them for scientific and societal benefit.”
By using these guanidinium-rich transporters, Wender says, he anticipates that researchers can learn more about how algae operate at a molecular level, such as how they fix carbon dioxide (a greenhouse gas), generate hydrogen (a clean fuel that combusts to produce water) and capture solar photons (solar energy applications). They also could be used to address environmental pollution problems, because they may be able to scavenge toxic molecules. Algae also can be model organisms for drug discovery. Wender thinks that the ramifications of being able to molecularly manipulate algae will be “quite broad,” and open up “a gateway for the exploration of a world that previously was difficult to access.”