Cell-to-cell variation in gene expression can result in distinct cell states, or modes of cell behavior. Ultimately, the information for creating cell states, and transitions between them, has to come from the genome. While we know a lot about how changing the sequence of DNA can impact the level (mean) of gene expression, we know very little about how DNA sequence can impact the heterogeneity (variance) of gene expression. Our hypothesis is that particular regulators have evolved to drive cell-to-cell variation across populations of cells. This variation occurs even if the environment of the cell is held perfectly constant. We are particularly interested in "all-or-nothing" effects that can arise from enhancers, transcription factors, signaling cascades, or other regulatory motifs.
