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Slime mold race could provide insights into disease

microfluidic mazes that the cells had to navigate race day at builing 114 of the Charlestown Navy Yard, Charlestown, Mass. Mar. 21, 2014.

courtesy of MGH Photography

Microfluidic mazes that the cells had to navigate race day at the Dicty World race, held at Massachusetts General Hospital

The race set off late in the afternoon on Friday at Massachusetts General Hospital: 15 competitors from across the world gathered for a neck-and-neck journey through a twisting maze, with a long straightaway that was the perfect setup for a sprint finish.

It was the World Dicty Race, a competition that unfolds on a microscope slide carved with tiny channels for a track. Each racer -- either a soil-dwelling slime mold called Dictyostelium or a type of human leukemia cell -- had been precisely genetically tweaked to give the greatest chance of navigating the course faster than the others.

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Over two hours, the race unfolded as spectators checked in by microscope and stitched together time-lapse video. Cells careened in slow motion around a course that stretched nearly a millimeter in length. A Dutch team took first place, closely followed by a team from the United Kingdom, and then by a team of Germans. Homegrown talent from Mass. General took a close fourth.

“The movement is about six orders of magnitude less than what we are used to in real life -- a person walking or running,” said Daniel Irimia, an assistant professor of surgery at Harvard Medical School who organized the contest. To put it in perspective, he said, “if you think about humans, what is six orders of magnitude faster? That’s the speed of light.”

The Dutch team, winner of the $5,000 grand prize, genetically tweaked a slime mold to make extra amounts of a protein that amps up signaling pathways involved in movement. The fourth-prize winner, Michael Myre of Mass. General, said that he had knocked out a gene called CLN3 that is of interest because it is often mutated in a rare developmental neurological disorder in children.

Myre admits that, of course, he would have liked to win, but regardless, he said, the race was a triumph for scientists who study slime molds -- a name that he is quick to note has fallen out of favor, replaced by the more accurate term, social amoeba. The event showed the power of using simple cells to probe fundamental biology and apply the insights to big questions in human health.

The question of how cells move around -- how they know where to go and what makes them move faster or slower or stay in place -- is poorly understood, though it is essential for grasping numerous aspects of human biology and disease. After trauma or a burn, immune cells must migrate to the site of injury. In cancer, cells that move around the body too much may seed other tumors. In the brain, cells must migrate to the right spots during development and even during adulthood.

Irimia said his interest has been in what makes white blood cells less efficient at migrating to a disease site after injury. If it’s possible to understand the molecular reasons for differences in that behavior, he said, it might be possible to find a drug that could trigger more efficient homing behavior. One day, it might be possible to treat injuries by boosting the body’s natural repair mechanisms. Alternately, in cancer, it might be useful to know how to handicap cells’ movements.

Myre been interested in learning how various genetic mutations affect the mobility of cells -- in the hopes that this might reveal something about how neurodegenerative disease occurs. Throughout a person’s life, neurons migrate into the hippocampus, the memory center of the brain. It’s possible that errors in migration or cell movement could play a role in causing neurodegenerative diseases of aging. And perhaps some developmental neurological diseases stem from brain cells that don’t go to the right place at the right time to build the parts of the brain we need to think and perceive things.

“With all the competitors, we can learn from the winners, because those are the genes that confer gain of function, that make the cell do something more,” Myre said. “But we can also learn from the losers, that can’t even get their cells into the maze.”

The results of the competition are here, but the true fruits of the competition -- a scientific paper that provides insights into what makes cells move faster and slower -- will be forthcoming.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.
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