Supplementary MaterialsS1 Movie: Movie of winning Dicty cells from Team 12. minutes. Cells were labeled with CellTracker? Green (Life Technologies) and the fluorescence channel is shown in green.(AVI) pone.0154491.s003.avi (4.2M) GUID:?5C4F018F-FC7E-475B-B8E1-332CF3C4F3CB S4 Movie: Movie of control HL60 cells. Control HL60 cells are shown traversing the maze racecourse. Time is shown in minutes. Cells were labeled with CellTracker? Green (Life Technologies) and the fluorescence channel is shown in green.(AVI) pone.0154491.s004.avi (3.5M) GUID:?F7E5B5AB-139B-4063-8E64-7276157D8884 Data Availability StatementData are available at https://figshare.com/s/ebf97b9cf877696dc20a. Abstract Chemotaxis is the ability to migrate towards the source of chemical gradients. It underlies the ability of neutrophils and other immune cells to hone in on their targets and defend against invading pathogens. Given the importance of neutrophil migration to health and disease, it is crucial to understand the basic mechanisms controlling chemotaxis so that strategies can be developed to modulate cell migration in clinical settings. Because of the complexity of human genetics, and HL60 cells have long served as models system for studying chemotaxis. Since many of our current insights into chemotaxis have been gained from these two model systems, we decided to compare them side by side in a set of winner-take-all races, the Dicty World Races. These worldwide competitions challenge researchers to genetically engineer and pharmacologically enhance the model systems to compete in microfluidic racecourses. These races bring together technological innovations in genetic engineering and precision measurement of cell motility. Fourteen teams participated in the inaugural Dicty World Race 2014 and contributed LP-211 cell lines, which they tuned for enhanced speed and chemotactic accuracy. The race enabled large-scale LP-211 analyses of chemotaxis in complex environments and revealed an intriguing balance of speed and accuracy of the model cell lines. The successes of the first race validated the concept of using fun-spirited competition to gain insights into the complex mechanisms controlling chemotaxis, while the challenges of the first race will guide further technological development and planning of future events. Introduction Neutrophils are our first line of defense against invading pathogens. They are recruited to the site of wounds, kill bacteria and fungi CD295 via various LP-211 mechanisms [1] and signal via cytokines to help coordinate LP-211 the immune response [2, 3]. Crucially, these defense mechanisms are only effective in warding off infection if neutrophils are able to move swiftly and accurately to the site of the wound in the first place. Indeed, in clinical settings where neutrophil motility and chemotaxis are impaired, patients are at a high risk for infection [4, 5]. In other conditions, overzealous neutrophilic infiltration can unnecessarily damage normal tissues [6, 7] and impair organ function, e.g. in acute respiratory distress syndrome [8], arthritis [9], ischemia-reperfusion injury [10], or aging [11]. Despite the clear importance of neutrophil migration in many diseases, little is known about how to enhance or inhibit migration for therapeutic use in alleviating many of these conditions [12]. Neutrophils and other immune cells crawl in a manner very similar to amoeboid protozoa, by coordinated protrusions and retractions of a dynamic cytoskeleton. Immune cells and amoeba also share similar mechanisms of steering their motion up or down chemical gradients in a process called chemotaxis. The social amoeba (Dicty) has proven a valuable and genetically tractable model system for understanding the fundamental mechanisms of neutrophil motility and chemotaxis [13, 14]. An equally important model system is the human promyelocytic cell line, HL60, which differentiates into neutrophils following treatment with dimethyl sulfoxide [15C17]. Decades of research in these systems have led to the discovery of many of the molecular components of the chemotaxis network and have shown that they are surprisingly well conserved between and humans [18]. While much has been learned about how to disrupt chemotaxis in these model systems [19], less is known about how to enhance it. Moreover, how the molecular components interact to give rise to cellular behaviors is complex [20] and integrating the results of different mutant studies to create a predictive model of amoeboid chemotaxis remains challenging, underlying the need for collaborative, larger-scale studies [21]. Finally, little is known about how to connect the behavior of cells in simple chemotaxis assays to the optimal performance of neutrophils fighting infection in complex environments. Towards the broad goal of enhancing neutrophil migration in conditions of disease by building on fundamental research in model systems, we started a worldwide competition, the Dicty World Race. LP-211 This competition challenged Dicty and HL60 researchers to apply their knowledge of chemotaxis to engineer the ultimate migrating cells to compete in a maze-like racecourse, which mimics the natural environment neutrophils move in. Unlike typical athletic competitions, genetic engineering and chemical doping were not only allowed,.