Advancing Epigenetics Towards Systems Biology

Tineke Lenstra

The Netherlands Cancer Institute, Division of Gene Regulation

Transcription dynamics

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tineke lenstra

Transcription in single cells is a stochastic process that arises from the random collision of molecules, resulting in heterogeneity in gene expression in cell populations. This heterogeneity in gene expression can influence cell fate decisions and disease progression. Out lab is interested in understanding the dynamics and mechanisms of stochastic transcription at a molecular level as well as their effect on the organism. 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 use cutting-edge single-molecule microscopy techniques to visualize individual protein and RNA molecules in living cells, providing direct quantitative measurements of the regulatory steps of transcription. These imaging assays are combined with novel gene-specific targeting approaches to modulate transcription of endogenous genes. By utilizing a combination of single-molecule microscopy, biophysical, genetic and molecular biology approaches to in both yeast and human model systems, we aim to understand the molecular mechanisms of transcription regulation, and how stochasticity in RNA synthesis modulates cell-to-cell variability and contributes to disease progression.