Racing amoeba across a microscopic maze is no doubt fun, but the reason scientists around the world are spending time and effort to breed the perfect contestants is because of its implications for disease and healing.
Research groups around the world working on cell-movement have been invited to participate in the second edition of the Dicty World Race, a microscopic Pac-Man of sorts where the contestants are cells, the race is a silicone maze, and the destination is a pool of a tasty chemical.
The challenge for the scientists is to create the line of cells that will be the quickest to traverse this maze. Unlike in typical athletic competitions, the organisers joke, genetic engineering and chemical “doping” are not only allowed but highly encouraged. This chemical-directed movement, called chemotaxis, is a crucial feature of immune cells in the body called neutrophils.
When a pathogen invades our body, these are the first to rush to the scene and defend against infection. Neutrophils navigate from the bloodstream by following the scent of specific chemical signals emitted by the enemy microbe. How well the neutrophil can exhibit this targeted movement determines how well the body can fight infection. On the other hand, overzealous neutrophils cause problems in diseases such as arthritis, where they enter joint tissues and cause damage and pain.
As much as we now understand the molecules that allow neutrophils to exhibit chemotaxis, we’re still unclear about how the different molecules work together. Hence, we have not been able to develop ways to enhance or inhibit neutrophil migration for therapeutic purposes. This is what led to the genesis of the first Dicty World Race, which took place at a lab at Harvard Medical School belonging to one of the organisers, Daniel Irimia, in 2014.
The first time around, participants were allowed to use either of two types of cells, Dictyostelium ‘Dicty’ amoeba (commonly known as slime mould) or a line of human cancer cells called HL60. These two types of cells are established models for human neutrophil cells, which themselves are difficult to study using typical lab tools. Dicty cells and HL60 have the added advantage of being relatively easy to genetically meddle with.
Many ways to win
For a cell to complete the maze and emerge victorious, its speed is not the only thing that matters. In fact, the winners of 2014’s race weren’t the ones that were the fastest but the ones that were willing to sacrifice speed for precision. The winning Dicty cells, from Team 12, were engineered to have an over-active ric8 gene, which enabled them to be more intelligent in navigating by sniffing out and moving toward regions of higher concentrations of the chemical bait. Though this slowed them down somewhat, Team 12’s slow but steady cells dominated, comprising 48 of the first 100 cells to cross the finish line.
Second in place were the HL60 cells from Team 4 which employed a contrasting strategy. Engineered to be more flexible and contract more easily, these cells were among the fastest cells to participate. However, their technique was much cruder and less directed, likely costing them the top rank. Team 4’s cells comprised 19 of the top 100.