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Gene Regulation: Tineke Lenstra

Transcription dynamics

Our lab is interested in understanding the mechanisms of transcription regulation in eukaryotic cells. In the last half century, our knowledge of gene expression has greatly advanced, but the majority of measurements come from large populations of cells. However, as a result of the stochastic nature of transcriptional process itself, cells can exhibit considerable heterogeneity in transcriptional responses. This stochastic gene expression variation can influence essential cell fate decisions, such as the decision to go into apoptosis. Diseases such as cancer often start when individual cells start acting aberrantly, illustrating the importance of single-cell approaches to study biological processes.

We use single-cell imaging approaches to understand the mechanisms of gene expression regulation in both yeast and human model systems. We employ 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. 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. Our imaging assays are combined with novel gene-specific targeting approaches to modulate transcription of endogenous genes. For example, we used time-lapse single-molecule imaging of sense and antisense (non-coding) transcription in living cells in tandem with strand-specific transcriptional blocking of the ncRNA by CRISPR/dCas9 to interrogate the role of ncRNA transcription in the yeast galactose response. By studying transcription dynamics in single cells 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.

Co-workers

Brouwer, Ineke

Ineke Brouwer

Postdoc

Experience

In 2011, I graduated as a MSc in Physics from the Vrije Universiteit in Amsterdam. Subsequently, I did a PhD in single-molecule biophysics at the Vrije Universiteit in Amsterdam which I completed in 2016. During my PhD I used a combination of optical trapping and fluorescence microscopy to study different biological processes. I joined Tineke Lenstra's group in 2017 studying transcription regulation in live cells.

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Balwierz, Aleksandra

Aleksandra Balwierz

Technician

Experience

I graduated from Jagiellonian University in Krakow, Poland with a master's degree in Medical Biotechnology. After gaining research experience in structural biology and epigenetic laboratories, I joined the graduate school at German Cancer Research Center in Heidelberg, where I studied the role of miRNAs in cancer cell signaling. In 2016 I joined Tineke Lenstra's group as a technician where I will participate in the study of transcription dynamics in eukaryotes using cutting-edge single-molecule microscopy techniques.

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Key publications View All Publications

  • Single-Molecule Imaging Reveals a Switch between Spurious and Functional ncRNA Transcription

    Mol Cell. 2015 Nov 19;60(4):597-610

    Lenstra TL, Coulon A, Chow CC, Larson DR

    Link to PubMed
  • Transcription Dynamics in Living Cells

    Annu Rev Biophys. 2016 Jul 5;45:25-47

    Lenstra TL, Rodriguez J, Chen H, Larson DR

    Link to PubMed
 
 

Recent publications View All Publications

  • Single-Molecule mRNA Detection in Live Yeast

    Curr Protoc Mol Biol. 2016;113:14.24.1-14.24.15

    Lenstra TL, Larson DR

    Link to PubMed
  • A high-resolution gene expression atlas of epistasis between gene-specific transcription factors exposes potential mechanisms for genetic interactions

    BMC Biol. 2015 Dec 23;13:112

    Sameith K, Amini S, Groot Koerkamp MJ, van Leenen D, Brok M, Brabers N, Lijnzaad P, van Hooff SR, Benschop JJ, Lenstra TL, Apweiler...

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Corsetto

  • E-mail

    s.corsetto@nki.nl

  • Telephone Number

    + 31 20 512 1970

Suzanne Corsetto
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