Gene expression is a tightly regulated process to ensure that genes are activated in the right cell at the right time. In the last half century, our knowledge of gene regulation has greatly advanced, but the majority of measurements come from large populations of cells. However, individual cells in a population can exhibit considerable variability in transcriptional responses, arising from the random collision of molecules. This stochastic gene expression variation can influence important cell fate decisions and can also contribute to heterogeneity in tumors.
Our lab aims to understand the mechanistic basis of stochastic gene expression variation by studying dynamics of gene expression at the molecular level in single cells. We employ and develop cutting-edge single-molecule microscopy techniques to directly visualize the behavior of individual protein and RNA molecules in living cells. We are interested in every cellular component or process that may regulate transcription, including promoter and enhancer sequences, gene-specific transcription factors, chromatin regulators, 3D genome architecture, ncRNA transcription, and the binding kinetics of the transcriptional machinery to the DNA.
We combine our live-cell microscopy methods with biophysical, genetic, molecular biology and computational approaches in both yeast and mammalian model systems. Our ultimate goal is to understand the molecular mechanisms of transcription regulation in single cells, and how stochasticity in transcription modulates cell-to-cell variability and contributes to cancer progression.