AsianScientist (Feb. 28, 2018) – The Mexican axolotl wears a perpetual, almost beatific smile. And why not, considering what this salamander is capable of? If it loses a limb (a not uncommon occurrence, since axolotls have a tendency to cannibalize one another) it can grow another—bones, muscles, nerves and all—in the space of a few weeks. If its heart gets damaged, it can regenerate cardiac tissue that is fully functional. Even severing its spinal cord won’t stop the axolotl—it simply repairs it and carries on doing whatever it is that salamanders do.
No other animal has superpowers to this extent. Luckily, although axolotls are critically endangered in the wild, they are relatively easy to breed in captivity. Scientists have been studying them in the laboratory for more than 150 years to try and understand their regenerative abilities at the cellular and molecular level, using them as a model for figuring out how these processes might work in humans.
This month, their efforts got a huge boost when the axolotl genome—the first salamander genome ever sequenced—was published in the journal Nature. At 32 billion base pairs, it is the largest genome sequenced to date, more than ten times bigger than the human genome and chock-full of repetitive sequences. To decode it, the study’s authors had to use sequencing techniques that generate very long reads, as well as develop new computational methods for piecing millions of reads together.
Before this, biologists studying axolotls would have had relatively little to go on compared to scientists who work with more traditional model organisms like yeast, flies and worms. But as laboratory and bioinformatics methods for sequencing and assembling complex genomes improve, non-traditional model organisms—of which the axolotl is only one of many—could soon become more widely adopted.
Fantastic laboratory beasts
While many excellent resources such as databases, strain catalogs and molecular tools are available for standard model organisms, these organisms are not always the best ones for studying a particular biological process. For example, while scientists have learned a lot about developmental biology from studying worms and flies, these animals don’t have the regenerative capabilities of axolotls.
But there are a number of better alternatives for studying regeneration and other similarly “hard-to-reach areas of biology,” write the authors of a 2017 BMC Biology forum article on non-traditional model organisms. Touching on diatoms that form glass cages around themselves, unicellular protists that contain 16,000 chromosomes, tardigrades that are unfazed by the vacuum of space and more, the article reads more like the script of the next installment of Fantastic Beasts and Where to Find Them than an academic treatise (and that’s a compliment).
One challenge for the use of non-traditional model organisms is that major genome centers tend to be less willing to sequence organisms that only a handful of researchers are working on. Fortunately, DNA sequencing is becoming cheaper and more accessible all the time, making it possible for individual labs, or a few collaborating ones, to take on the sequencing and assembly themselves, write the authors.
Take, for example, the giant single-celled ciliate Stentor coeruleus (Stentor)—a freshwater pond organism that is ideal for studying regeneration and pattern formation. Like the axolotl, Stentor has regenerative superpowers, but at the single-cell level—cut one Stentor in half and both halves will grow back into normal cells. Its genome was established in 2017 thanks to a “DIY approach” undertaken by two University of California, San Francisco labs and their expert collaborators.
Once the genome of a fantastic beast is available, many more doors open. Experimental tools such as RNA interference and CRISPR can be developed to test the function of interesting genes, giving scientists more insights into the biological process in question.
To science fiction and beyond
In addition to helping scientists understand fundamental biological processes, non-traditional model organisms can also inspire the development of new technologies. For example, certain bacteria produce coiled ribbons of protein called R bodies, which can extend in a telescoping fashion to deliver toxins to other organisms. These unique molecules are being studied as a nanobiotechnology model system, and could be used to develop methods of delivering payloads such as DNA or drug molecules to cells.
Non-traditional models can even take us into the realm of science fiction. Tardigrades, which can endure extreme environmental conditions, and killifish, whose embryos can survive months of drought, could perhaps teach us a thing or two about suspended animation.
At the end of the day, no matter how strange these organisms are, their use as model organisms means that scientists are not studying them merely for the sake of these curiosities, but with a larger, more universal goal in mind.
“These organisms aren’t being studied because they are weird, or because of a fondness for biodiversity, but because they make it easier to ask central questions about biology that have remained unanswered to this day,” write the authors.
This article is from a monthly column called The Bug Report. Click here to see the other articles in this series.
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Copyright: Asian Scientist Magazine; Photo: Shutterstock.
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