By Raleigh McElvery
Meet Hydra: classical model system for regeneration research and “immortal” organism. Since “immortal” implies quite a lengthy duration, researchers are careful to add a disclaimer: This tube-like animal simply has no documented limits to its lifespan. In fact, one team of scientists has been observing a single batch of Hydra for the past 12 years in hopes of defining that limit, but still no luck; the tentacled animals are no worse for the wear than they were on day one.
The same cannot be said for these scientists who, irrespective of the time of day or holiday, take great care to preserve their original Hydra specimens, continually discarding offspring clones (or “buds”) as they detach from the parent.
Mapping the Hydra nerve net and behavior
Rafael Yuste of Columbia University, who also teaches at the Marine Biological Laboratory in the summer, aims to develop Hydra as a model system in which scientists can observe changes in neural activity and behavior simultaneously and in real time. It could then be possible to “decipher the neural code”—in other words, to understand the electrical patterns that give rise to certain behaviors, and to predict what the animal will do next.
To do this, Yuste’s laboratory has collaborated with Steele and developed a method to measure the activity of the entire Hydra nerve net at the same time. It is a novel application of calcium imaging, which uses a fluorescent marker to track the flow of calcium within neurons, indicating which neurons are active and when.
“Individual neurons aren’t as important as entire neural circuits,” says Yuste. “Metaphorically speaking, we need to examine more than just one pixel at a time to ascertain the entire picture.”
Yuste has also spearheaded the Brain Activity Map Project, a proposal that he and his colleagues made to the White House to develop technologies for large-scale studies of neural circuits in animal models and humans. His proposal has since led to the ongoing federal BRAIN Initiative.
— Raleigh McElvery
Steele isn’t referencing Hydra’s cloning process. Instead, he’s referring to the three separate cell types, or lineages, found in this animal. As these cells age or undergo damage, they are replaced by their stem cell “precursors,” leading to new cells and constant regeneration that may help explain why Hydra don’t seem to age.
A freshwater relative of jellyfish, Hydra possess a single, sticky foot at the base of a hollow body tube where the stem cells reside. Sprouting from the opposite end of the body tube is a ring of tentacles that surround the mouth. Two kinds of muscle cells constitute the body column, while the third cell type (interstitial) is interwoven with the muscle cells. The interstitial cell lineage gives rise to a dispersed nervous system called a “nerve net.” This same cell lineage also produces the stinging cells that Hydra use to capture prey, as well as gametes for sexual reproduction.
Since the muscle cells divide continuously, in order for Hydra to maintain its minute stature, all cells—including nerves—are eventually displaced to the animal’s extremities and fall off.
“It’s the equivalent of watching one of your cells migrate from your elbow to your fingernail,” Steele says.
In other words, Hydra are continuously being created anew. Because the cells are constantly changing position and role depending on current location, Hydra provide insight into the patterning process: that is, a cell’s ability to know where it is and what kind of cell to become based on its location. (Or what not to become, as the case may be, since interstitial cells never interconvert with muscle cells.)
Hydra cells seem to have this patterning process down pat. Researchers can cut a Hydra in half and the cells will simply re-assign their duties and produce two fully functioning, independent animals. Likewise, disassociating the cells from one another does not prevent them from re-aggregating and re-organizing to beget more Hydra.
Despite their patterning prowess, Hydra emerged early in the evolutionary tree and are still considered relatively primitive. “Scientists are always trying to find the simplest model to answer their research questions,” explains Steele. “We can compare Hydra to other more complex animals to see what life was like 600 million years ago.”
Hydra under the microscope
Hydra’s march to scientific study, spurred by observations by microscope inventor Antoni van Leeuwenhoek in 1702, was initially marked by fits and spurts. The Swiss naturalist Abraham Trembley used Hydra in the 1740s to record the first instance of animal regeneration, and his work was followed up at the MBL in the early 1900s by Thomas Hunt Morgan and members of his Columbia University lab, including Ethel Browne Harvey.
Yet it wasn’t until the late 1960s and early 1970s that Hydra re-emerged as a research model in modern biology—followed by yet another hiatus when fly and worm genetics surged to the forefront. Nevertheless, in 2010 Steele and colleagues successfully sequenced the Hydra (H. magnipapillata) genome, re-igniting the Hydra movement.
“After that, we knew how many genes there were and what they looked like,” recalls Steele. “Once we began manipulating the genome and creating transgenic Hydra, we were back in the game. Today Hydra are even studied in MBL courses.”
Hydra’s cellular resiliency enables them to tolerate all manner of genetic perturbations, from the addition of tentacles to the removal of their entire nervous system. Steele surmises Hydra will be ideal for the up-and-coming field of synthetic biology, where scientists genetically engineer organisms to suit various research interests. He hopes to one day “paint” Hydra, prompting cells to express colored proteins that permit easy visualization in normal light.
On earth since the dawn of the nervous system and still explored by scientists today, Hydra may be immortal in more ways than one.