Searching for Network Laws in Slime

Of all science’s model organisms, none is as weird as Dictyostelium discoideum, a single-celled amoeba better known as slime mold. When they run out of food, millions coalesce into a single, slug-like creature that wanders in search of nutrients, then forms a mushroom-like stalk, scatters as spores and starts the cycle again. In the rules governing […]

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Of all science's model organisms, none is as weird as Dictyostelium discoideum, a single-celled amoeba better known as slime mold. When they run out of food, millions coalesce into a single, slug-like creature that wanders in search of nutrients, then forms a mushroom-like stalk, scatters as spores and starts the cycle again.

In the rules governing the behavior of these creatures, researchers hope to find analogues for baffling biological mysteries, from the specialization of cells to how animals become altruistic.

"What I look for is principles that work on different scales," said Princeton University biologist Ted Cox, who in an upcoming Nucleic Acids Research paper describes how cellular proteins find their DNA targets, a process he links to the slime mold's foraging patterns. "The theoretical underpinning is exactly the same."

Research on Dictyostelium took off in the 1950s, when work by Princeton biologist John Bonner led to the discovery of a chemical used by slime mold cells to signal, triggering their group-forming behavior. At the time, scientists assumed that a few specialized cells controlled the process. But a couple decades later, inspired by famed mathematician Alan Turing's work on how simple rules produced complex structures, researchers showed that slime complexity resulted from the linked interactions of its cells, not some centralized regulator.

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Physarum polycephalum, the other slime mold, is just a single cell containing multiple nuclei. It can swell to enormous sizes, covering an entire square foot, and it's full of surprises.

In a paper published Monday in the Proceedings of the National Academy of Sciences, researchers showed how Physarum is even better at maintaining a balanced diet than humans.

In January, researchers described how it found ultra-efficient routes between food arrayed like Japanese cities. (The same trick has also been performed with English roadways.)

Researchers have also found that Physarum possesses memory, and think its computational powers can be harnessed in biological computer form.

Said Toshiyuki Nagaki, the Hokkaido University scientist who ran Physarum around a model Tokyo, it's time "to reconsider our stupid opinion that single celled organisms are stupid."

Their research stirred an ongoing scientific fascination with emergent properties and complexities. Since then, however, Dictyostelium has been overshadowed by Physarum polycephalum, another amoeba that exhibits amazing networking properties and is also known as a slime mold, though it's no closer to the other slime mold than a horse is to a frog. (See sidebar.) To the chagrin of Dictyostelium researchers, the two creatures are sometimes confused with each other.

But though the spotlight has moved, Dictyostelium research continues. Most of it has shifted from big-picture work to fine-grained focus. Dictyostelium's genome was sequenced five years ago, and information about its genetic and molecular mechanisms has steadily accumulated. From the application of modern mathematical modeling techniques to these realms of node-by-now measurement, the rules of networks may finally emerge.

"Fifty or 60 years ago, ecology was a fantastic collection of facts about organisms. Then along came Robert Macarthur, who used very simple equations to suggest how all this diversity might have occurred," said Bonner, whose book The Social Amoebae was published in November. "That opened up a whole new way of thinking about the outside world. And I think that is going to happen with slime molds."

According to Cox, the same dynamics governing slime mold signaling likely explain how calcium levels are synchronized — or go haywire — during the beating of a heart, or during embryonic development. The same goes for fluxes of mood-regulating neurotransmitters.

"It's a unifying theory of excitable systems," said Cox, who also noted that vortex patterns mapped in aggregating Dictyostelium cells are replicated in the spread of pathogens. Indeed, the slime mold is a useful model for studying the transmission dynamics of many diseases, from cholera to tuberculosis.

Cox's upcoming paper is the latest in a series of papers on how gene-activating proteins move from one section of DNA to another. Such coordination can be visualized on a larger scale as a pinhead floating in a large room, and landing randomly on a pin. For all practical purposes, it should be impossible, but Cox sees a hint to an answer in how the slime mold "slug" searches for food.

"It's Einstein's diffusion equations, in three dimensions," he said.

Before the slug searches for food, it has to form. Those dynamics are the focus of Rice University evolutionary biologist Joan Strassman. As described most recently in an October Nature paper, Strassman's work shows how gene mutations that allow individual amoebae to cheat inevitably cause damage to other, essential cell systems.

Called "positive pleiotropy," it's a built-in system for ensuring altruistic cooperation, a phenomenon that fascinates biologists. "The microorganisms that help and hurt us are all talking to each other. There are social interactions going on in the bugs in our skin," said Strassman. "This can tell us things about how microbes interact."

For a "so-called simple organism," said North Carolina State University biologist Larry Blanton, "it's doing a lot of sophisticated things of relevance to higher organisms."

Images: 1) At left, the life cycle of Dictyostelium/Larry Blanton. At right, a spiraling pattern of chemical signaling/Marcus Hauser. 2) Physarum* spreading across England, from Andy Adamatzky's "Road planning with slime mould: If Physarum built motorways it would route M6/M74 through Newcastle."*

See Also:

Brandon Keim's Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecological tipping points.