Cells make critical decisions such as whether to proliferate or die by constantly evaluating their internal and external environment. Understanding how cells make these decisions is still an open question that can be addressed by combining quantitative biology and mathematical modelling. This project tackles long standing questions in cell fate determination by using a new technology that allows measuring biochemical changes inside individual cells in real time as they make decisions. The interdisciplinary nature of this project, combining molecular and cell biology, protein engineering, advanced imaging, and mathematical modeling, makes it particularly well-suited for educational purposes. This will foster a unique training environment to introduce high school, undergraduate and graduate students to the field of single-cell quantitative biology.
MAPKs are key signaling molecules that orchestrate cellular responses to a diverse array of stimuli through a signaling network that ultimately controls gene expression, cell cycle or cell migration. The current understanding of how this highly interconnected network controls cellular decisions is incomplete because of: (i) a lack of methods to quantify the activity multiple signaling proteins in real time and (ii) the use of cell population assays that average unsynchronized single cell behaviors. To address this need, this project will pioneer a new generation of biosensors that allow simultaneous quantification of multiple protein activities in thousands of live single cells. The central hypothesis is that the signaling equilibrium between MAPKs is critical to regulate single cell outcomes (i.e. proliferation, quiescence, senescence, apoptosis). Using endpoint cell fate analysis, the researchers will be able to dissect the signaling patterns that underlie cell fate choices. In combination with mathematical modelling, this project aims to understand the fundamental principles of MAPK signaling dynamics that govern cellular decision making.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
