The Center for Systems Biology is one of the National Centers for Systems Biology funded by the National Institute of General Medical Sciences (NIGMS). The Center, located at the Institute for Systems Biology (ISB) in Seattle, Washington, is composed of three integrated research projects unified by the question: How do cells transition from state A to state B?
The reality of biological systems is that there is a dynamic interplay between molecular networks that leads to complex phenotypes. Transitions between states are also mediated by molecular networks. Although gene regulatory networks, signaling networks, or metabolic networks tend to be studied one network at a time, a systems view of biology demands that we measure and model the dynamic interplay among the hierarchy of molecular networks to make predictions. In Project 1, yeast and archaea responding to environmental stimuli are used to develop tools and approaches for network integration and phenotype prediction. Typically in these studies we use large populations of genetically identical cells to measure molecular species (e.g., mRNA or protein) which are then used for model inference or as parameters for mechanistic models. This is an approximation that ignores the presence of multiple cell states within the population and may be misleading with respect to the trajectory each cell takes as it transitions from one state to another. In Project 3, cardiomyocytes and breast cancer stem cells are being used to develop approaches for studying single cell dynamics and critically address the contributions of quantized cells states in the differentiation process. And finally, when cells assemble into organs, or multicellular assemblies, cells adopt specialized roles to support the assembly. In Project 2, yeast colony formation is being used to understand and model multicellular assembly processes.