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A Mathematical Model Reveals Long-Distance Cell Communication Mechanism
How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping? A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Krešimir Josić at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology. Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities. The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator. Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, “That’s why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules.” Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells. The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. “It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That’s why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time,” said Professor Kim. Professor Kim added, “Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics." The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research. (Figure: Complex molecular interactions among microbial consortia is simplified as interactions among points on a limit cycle (right).)
Soul-Searching & Odds-Defying Determination: A Commencement Story of Dr. Tae-Hyun Oh
(Dr. Tae-Hyun Oh, one of the 2736 graduates of the 2018) Each and every one of the 2,736 graduates has come a long way to the 2018 Commencement. Tae-Hyun Oh, who just started his new research career at MIT after completing his Ph.D. at KAIST, is no exception. Unlike the most KAIST freshmen straight out of the ingenious science academies of Korea, he is among the many who endured very challenging and turbulent adolescent years. Buffeted by family instability and struggling during his time at school, he saw himself trapped by seemingly impenetrable barriers. His mother, who hated to see his struggling, advised him to take a break to reflect on who he is and what he wanted to do. After dropping out of high school in his first year, ways to make money and support his family occupied his thoughts. He took on odd jobs from a car body shop to a gas station, but the real world was very tough and sometimes even cruel to the high school dropout. Bias and prejudice stigmatizing dropouts hurt him so much. He often overheard a parent who dropped by the body shop that he worked in saying, “If you do not study hard, you will end up like this guy.” Hearing such things terrified him and awoke his sense of purpose. So he decided to do something meaningful and be a better man than he was. “I didn’t like the person I was growing up to become. I needed to find myself and get away from the place I was growing up. It was my adventure and it was the best decision I ever made,” says Oh. After completing his high school diploma national certificate, he planned to apply to an engineering college. On his second try, he gained admission into the Department of Electrical Engineering at Kwang Woon University with a full scholarship. He was so thrilled for this opportunity and hoped he could do well at college. Signal processing and image processing became the interest of his research and he finished his undergraduate degree summa cum laude. Gaining confidence in his studies, he searched around graduate school department websites in Korea to select the path he was interested in. Among others, the Robotics and Computer Vision Lab of Professor In-So Kweon at the Department of Electrical Engineering at KAIST was attractive to him. Professor Kweon’s lab is globally renowned for robot vision technology. Their technologies were applied into HUBO, the KAIST-developed bimodal humanoid robot that won the 2015 DARPA Challenges. “I am so appreciate of Professor Kweon, who accepted and guided me,” he said. Under Professor Kweon’s advising, he could finish his Master’s and Ph.D. courses in seven years. The mathematical modeling on fundamental computer algorithms became his main research topic. While at KAIST, his academic research has blossomed. He won a total of 13 research prizes sponsored by corporations at home and abroad such as Kolon, Samsung, Hyundai Motors, and Qualcomm. In 2015, he won the Microsoft Research Asia Fellowship as the sole Korean among 13 Ph.D. candidates in the Asian region. With the MSRA fellowship, he could intern at the MS Research Beijing Office for half a year and then in Redmond, Washington in the US. “Professor Kweon’s lab filled me up with knowledge. Whenever I presented our team’s paper at an international conference, I was amazed by the strong interest shown by foreign experts, researchers, and professors. Their strong support and interest encouraged me a lot. I was fully charged with the belief that I could go abroad and explore more opportunities,” he said. Dr. Oh, who completed his dissertation last fall, now works at the Department of Electrical Engineering and Computer Science at MIT under Professor Wojciech Matusik. “I think the research environment at KAIST is on par with MIT. I have very rich resources for my studies and research at both schools, but at MIT the working culture is a little different and it remains a big challenge for me. I am still not familiar with collaborative work with colleagues from very diverse backgrounds and countries, and to persuade them and communicate with them is very tough. But I think I am getting better and better,” he said. Oh, who is an avid computer game player as well, said life seems to be a game. The level of the game will be upgraded to the next level after something is accomplished. He feels great joy when he is moving up and he believes such diverse experiences have helped him become a better person day by day. Once he identified what gave him a strong sense of purpose, he wasn’t stressed out by his studies any more. He was so excited to be able to follow his passion and is ready for the next challenge.
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