Systems Biology of Single Cell Metabolism - overview
The goal of this project is to generate a single cell datasets for the analysis and development of computational tools in order to predict metabolic, transcriptional and macromolecular states in cells. Determining the state of a metabolic network in a cell and the regulation of enzymes enabling it, will be inferred through the spatial localization of fluorescently tagged enzymes in single cells.
The underlying argument is that the distribution of an enzyme in the cytoplasm mirrors its activity state. We will further measure using fluorescent time-lapse microscopy the rates of single cell growth, DNA replication and analyze how gene-circuits regulate these states. In-house whole cell computational models and methods developed through the Dialogue on Reverse Engineering Assessments and Methods (DREAM) will be used to explore the relationships between metabolism, gene expression and parameter estimation. As shown in the B.subtilis movie below, we want to understand how cells having same genomes and same external conditions of growth make different decisions.