Thursday, 30 January 2014 00:00

Speeds May Top 153 Years per Mile in Great Dicty Vs. Neutrophils Road Race

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dictyRacing dicty.
Illustration by Johnny Chang.
Amoebae, start your engines. Dictyostelium discoideum a.k.a. Dicty, the slime mold with a vast reputation (and literature) as an experimental model system, will go head to head (or leading edge to leading edge) next May against a neutrophil challenger, a human neutrophil-like cell line called HL-60, in a desperate race through a microfluidic maze. The winning cells will get a drink of chemical attractant and their human managers cash (amount undetermined but likely small) and fame (fleeting).

Speeds could be dazzling. Race organizers say that the average single cell Dicty roars along at 10-20 microns a minute. Calculators at the ASCB National Office predict that a multi-generational relay team of speeding Dicty would take 153 years to cover a mile (or 95 years for a kilometer).

The "Dicty Vs. Neutrophils" race, which is being billed as "one billion years of evolution" in the making, is an outgrowth of the original World Cell Race first held in 2011 and featured at the ASCB Annual Meeting that year in Denver. The 2014 running will take place May 16 in the Massachusetts General Hospital (MGH) lab of Dan Irimia. Entrants (cells) will be shipped in from around the Dicty world and raced against the clock. Time-lapse video will record the heats. The winner (human) will most likely go on to the Annual International Dictyostelium Conference in Potsdam, Germany, in August to collect a trophy and the admiration of peers.

Irimia says that the first World Cell Race featured cancer cells but brought in inquiries from keepers of other cell lines. Monica Skoge, a postdoc at the University of California, San Diego, and a devoted member of the Dicty community, contacted Irimia about a Dicty competition and then enlisted Chris Janetopoulos, a cell biologist (with Dicty roots) who collaborates with biophysicists at the Vanderbilt University School of Medicine, to work out protocols for racing cell prep and designs for the microfluidic race course.

This is one race where the organizers are actively encouraging "doping," says Skoge, though using genetics instead of drugs. Until now, the search for Dicty motility mutants has largely concentrated on finding those with problems in chemotaxis (directed movement). A winning Dicty entry will have to be faster than your average soil-dwelling slime mold. Dicty labs are encouraged to genetically tune up overlooked speedy mutants or to take synthetic biology into their own hands and create a road running Dicty demon. "This is a new way of thinking," Skoge says.

The designers, though, face a trade-off in their Dicty engineering between speed and accuracy, says Skoge. A speedier Dicty might burn up the microfluidic track but not be able to sense the cAMP chemo-gradient accurately and end up going in the wrong direction. On the other hand, the faster Dicty could leave an overly cAMP-sensitive Dicty in the dust (or fluid).

Irimia, whose lab will be fielding a competitive HL-60 racing stable, thinks it will be a close contest. "Dicty is slower but it's more precise in picking up the direction of a gradient where HL-60, which is a neutrophil-like cell line, is fast but not very precise. The challenge for the race is to modify either the Dicty or the HL-60 cell line to make them faster or more directional."

But there is a serious purpose behind the event, says Irimia. "What we're trying to do here is to have the people from the biology side and the people from the engineering side (together) so we can bring more tools to the race." Cell migration is a rapidly maturing field where Irimia sees exciting clinical applications just over the horizon. Yet he says that biology researchers are still using many lab tools developed in the 1960s that now present barriers to better measurement, faster operations, and scalability. Designing racing cells could encourage biologists to think more about what they want to measure and give bioengineers clearer goals to pursue, he believes.

Understanding cell migration will have real applications in medicine, Irimia contends. "For example in cancer, it would be ideal to stop the movement of cancer cells and stop metastasis so we could then deal with the cancer in a more effective way. Also if you look at the top 10 diseases in the world, seven of them are related to chronic inflammation. When you say inflammation, then you are talking about immune cells including neutrophils, which move from the blood to tissue. We need drugs to stop this movement that happens with inflammation but we don't want to stop this movement completely because (then) we'd become unprotected from microbes. So there's this tricky situation in places where cell migration takes place."

The Dicty Vs. Neutrophils race is also aimed at the general public, says Irimia who hopes that it will get play in the news and social media. "It's really easy to understand movement. It's ingrained in our brains," he says. "We see something moving, we pay attention to that. So this is a way of promoting science to the general public by saying that in science, we only know this much and we need to learn more to make an impact on health. With the whole situation with science funding today, it's an important message to get out."

The challenge for the race organizers, says Janetopoulos, is ensuring a level playing field. "The difficulty is how do you get everybody's cells prepared properly so it's a fair race," Janetopoulos explains. "You need to get all the cells into the same stage. With Dicty, you starve them for 5-6 hours and then they polarize [start directionally migrating] but we think that a few people will be sending mutants that polarize at different rates." The preparation protocols have to be designed so that polarization rates aren't a factor in the race, says Janetopoulos. A similar protocol has to be worked out for the HL-60 neutrophils, which are slightly more difficult to work with.

But which cells are going to win? Irimia claims strict neutrality. His lab, after all, is staging the race. He points out that the Dicty vs. neutrophils debate is an old one. "Dicty is a very attractive model (system) because it is so easy to work with while HL-60 is closer to the human. The debate at cell migration meetings is always about which one is better? Which one will tell you more?"

Janetopoulos also thinks Dicty Vs. Neutrophils will be close. Although his background is in Dicty, he now collaborates with a Vanderbilt colleague on neutrophil experiments. He says that despite their evolutionary distance, Dicty and human-derived neutrophils have many conserved systems. Discoveries in one are often reported to have an analog in the other system within months. "We're really close together so we all know each other," says Janetopoulos. His only prediction, "There will be no hard feelings."



John Fleischman

John is ASCB Senior Science Writer and the author among other things of two nonfiction books for older children, "Phineas Gage: A Gruesome But True Story About Brain Science" and "Black & White Airmen," both from Houghton-Mifflin-Harcourt, Boston.

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