Our Focus

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. To understand the mechanisms and dynamics of gene expression in single cells, we use a range of single-molecule imaging techniques to directly observe the stochastic behavior of regulatory factors and the process of transcription, as these dynamically occur inside living cells. We combine these microscopy methods with gene-specific and conditional perturbations, (single-cell) genomic experiments, single-molecule in vitro analyses, and computational approaches, using both budding yeast and mammalian cells as model systems. With these powerful tools, the projects in the lab focus on different aspects of stochastic transcription regulation by: 1. transient DNA binding of transcription factors, 2. spatial clustering of transcription factors, 3. promoter and enhancer sequences, 4. chromatin remodeling, and 5. DNA supercoiling. For example, in a recent study, we showed how remodeling of different promoter nucleosomes regulate specific bursting properties. To push the field forward, we are also developing novel single-molecule microscopy techniques and kinetic analysis tools. Overall, by visualizing transcription dynamics in single cells, we aim to understand the mechanisms of stochastic transcription, and how this stochasticity in transcription modulates cell-to-cell variability and contributes to cancer progression.