QSB: Construction and Experimental Validation of Models of MAPK Signaling in Budding Yeast

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Successful development of the biotechnology industry holds great promise for improving health and quality of life of the people in this country and all over the world. The last decade has brought about the awareness of how complex and finely organized biological systems are. Even the simplest yet highly biotechnologically relevant organisms, such as bacteria and yeast, display an amazing degree of complexity in regulation of their life cycles. An essential part of this complexity is the function of their signaling pathways, the biochemical multi-molecular links between their genes and the environment. Understanding these biochemical links can help researchers to better control the way organisms behave and respond to the changing biotechnological needs. To investigate the complexity of signal transduction novel technologies are needed, the technologies that are rooted in our ability to quantitatively model the underlying processes and to precisely control cell behavior on the microscopic scale. This project is aimed at an integrated experimental and computational exploration of signaling pathways in yeast. This research will develop a novel, high throughput method for collection of data that will allow performing experiments with hundreds of individual cells exposed to a variety of conditions in the same microfabricated chip over extended periods of time. The results of these experiments will be analyzed using a detailed mathematical and computational model of the underlying signaling mechanisms. The model will then be used to guide further experimentation. This integrated approach will also be used to investigate the interaction between several signaling systems simultaneously exposed to multiple signaling stimuli changing in time and in space. The results of this research will lead to both a better understanding of the function of a biologically and biotechnologically important organism and to creation of a prototype system for understanding cell signaling in other living cells. Graduate students will be trained in this research, and this example of a tightly coupled study integrating theory and experiment will be used in courses taught at Johns Hopkins University and the University of California at San Diego, and potentially at other institutions. This approach may influence the way cellular signaling is studied by future scientists.