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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.

Positions available

We are continuously looking for talented postdocs, PhD students, technicians and master students. If you are interested in joining our lab, please send an enquiring email including your CV and motivation (and transcripts for PhD and master students) to Tineke Lenstra (t.lenstra AT nki.nl).

Co-workers

Atanasovska

Biljana Atanasovska

Postdoc

Experience

Trained as a biologist, I received my bachelor degree from the University Ss. Cyril and Methodius, Faculty of Natural Sciences and Mathematics in Skopje, Macedonia. In 2013, I graduated as a MSc in Health Sciences (Genetic Epidemiology) from the Erasmus Medical Center in Rotterdam. The same year I started my PhD training at the University Medical Center Groningen. My PhD research was focused on detecting and characterizing the role of long non-coding RNAs in liver diseases using transcriptomics, genomics and experimental approaches. In 2018, I joined the group of Tineke Lenstra to study the dynamics and mechanisms of eukaryotic transcription. 

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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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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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Coppola

Stefano Coppola

Postdoc

Experience

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Joossen

Linda Joosen

Technician

Experience

I graduated in 2008 with a Bachelors degree in Molecular Research. During my internship in Clinical Genetics, and later on work as a research technician and trainer in Cell Biology, I obtained a fascination for microscopy technologies and the capabilities with it in scientific field.
In 2019, I joined the group of Tineke Lenstra as a technician to study transcription regulation in living cells with the use of advanced single-molecule techniques.

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Marit de Kort

Marit de Kort

PhD student

Experience

I obtained my Msc in biomedical sciences at Utrecht University in 2019. My internships were performed at the labs of prof. Holstege at the Princess Maxima Center in Utrecht and of prof. Hochedlinger at the Massachusetts General Hospital in Boston. In 2020, I started my PhD in the lab of Tineke Lenstra, where I will study transcription dynamics in mammalian cells, using microscopy.

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Kuijntjes

Gert-Jan Kuijntjes

PhD student

Experience

I studied Cell Biology at Utrecht University and obtained my master's degree in 2018. After graduating, I joined the groups of Tineke Lenstra (NKI) and John van Noort (Leiden University) as a PhD student. In this shared project I will study the link between the transcription of genes and their DNA structure at single cell level.

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Meeussen, Jos

Jos Meeussen

PhD student

Experience

In 2017, I started a MSc in Molecular Life Sciences at Wageningen University & Research. During this study, I have developed a specific interest for the dynamics and biochemical mechanisms of protein-DNA interactions, as well as the single-molecule imaging techniques used to study these. This fascination has led me to the group of Tineke Lenstra for my internship, where I will use these imaging techniques to study transcription factor clustering in budding yeast.

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Patel

Heta Patel

PhD student

Experience

I received my bachelor's degrees in 2015 from the University of California, Santa Cruz in pure math and biochemistry and molecular biology. For the next two years, I did various internships at the National Institutes of Health, where I met my current supervisor, Tineke Lenstra. I joined her group in 2017 as a PhD student to study the effects of DNA topological constraints on transcriptional bursting.

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Pomp, Wim

Wim Pomp

Research Assistant

Experience

For a physicist as myself, biology provides a huge pool of interesting challenges which enhance our understanding of life, and generate exciting new physics. As such, I completed my PhD in Leiden in Thomas Schmidt's group by looking at the interaction between shape and biological function. After that I briefly worked on the retromer system, which recycles certain proteins. In Tineke Lenstra's group I will be employing a novel system which will give us insight in RNA transcription.

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Jessie vd Velde

Jessie van de Velde

master student

Experience

I am a master student at the Vrije Universiteit  in Amsterdam. Before starting my master's, I did the higher laboratory school in Amsterdam and the lower laboratory school in Beverwijk. This is my second internship at the NKI. I will be investigating the role of the SWI-SNF complex of s.cervisiae in regulation of transcription of the galactose responsive genes by using single molecule RNA FISH and PP7 technology to visualize individual RNAs within living cells.

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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

  • Visualizing transcription: key to understanding gene expression dynamics

    Curr Opin Chem Biol. 2019 Jul 5;51:122-129

    Brouwer I, Lenstra TL.

    https://www.ncbi.nlm.nih.gov/pubmed/31284216
  • Live‐cell imaging reveals the interplay between transcription factors, nucleosomes, and bursting

    EMBO J. 2019 May 17

    Donovan BT, Huynh A, Ball DA, Patel HP, Poirier MG, Larson DR, Ferguson ML, Lenstra TL.

    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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