Credit: Sanne Boersma, copyright: Hubrecht Institute

Tanenbaum: Gene expression dynamics

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The Tanenbaum group uses cutting-edge live-cell single molecule microscopy and new types of genetic engineering to uncover the molecular mechanisms of gene expression control in individual cells.

Our work focuses both on regulation of human genes in health and disease and on gene regulation of RNA viruses. Using our single-molecule approaches, we aim to uncover how the dynamics and heterogeneity in gene expression affects cell fate. In addition, we are developing new imaging technologies to visualize gene expression dynamics with ever increasing resolution to achieve a deep molecular understanding of these processes.

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Figure 1. Single molecule imaging of mRNA translation using the SunTag system. (A) Schematic of the SunTag fluorescence labeling strategy. (B) Imaging translation on single mRNA molecules in live cells.

Single-molecule analysis of gene expression in living cells

Previously, we have developed an imaging technique called “SunTag” (Tanenbaum et al., 2014, Cell), which allows us to link many GFPs to a protein molecule of interest (Fig. 1A). This GFP multimerization approach makes the fluorescence tags far brighter than was previously possible, and enables us to visualize complex biological processes with single molecule sensitivity in real-time in living cells. Using the SunTag, we have developed a method to visualize translation and degradation of single mRNA molecules in space and time (Fig. 1B) (Yan et al., 2016, Cell; Hoek et al., 2019, Mol Cell). We are employing these methods to visualize gene expression control in living cells with incredible precision and to uncover how regulatory mechanisms function at the single-molecule level. We are using a combination of quantitative single cell and single molecule fluorescence microscopy and computer simulations to look beyond cell population averages, and study how single cells tune gene expression over time and how differences in gene expression affect cell fate. For example, we have applied the SunTag translation imaging technique to study RNA quality control (Hoek et al., 2019, Mol Cell), heterogeneity in translation start site selection (Boersma et al., 2019, Cell) and post-transcriptional regulation of gene expression by small RNAs (Ruijtenberg et al., 2020, Nat Struct Mol Biol). More recently, we have developed Stopless-ORF circular RNAs (socRNAs) as a powerful new method to study individual ribosomes with very high resolution (Madern et al., 2025, Cell). We are currently exploring additional mechanisms of post-transcriptional gene regulation and are developing new technologies to examine gene expression control with even greater precision.

Visualizing translation, transcription and replication of single RNA viruses

RNA viruses are among the most prevalent pathogens worldwide and are a major burden on society. RNA viruses have been studied extensively, but surprisingly little is known about the processes that occur during early viral infection. The first hours of infection are likely very important, as the outcome of the infection (e.g. is the virus able to replicate? Can the host cell detect the virus and prevent its spreading before viral replication can occur?) may be determined at the early stages of infection. Lack of understanding of early infection is largely due to a lack of highly sensitive assays for viral detection, as during the early stages only one or a few viral RNAs are present per host cell. We have developed a single-molecule imaging assay based on our SunTag technology, called virus infection real-time imaging (VIRIM) that allows detection of single viral RNAs, which is therefore uniquely suitable to study early viral infection (Boersma et al, 2020, Cell). Using VIRIM we can detect the moment of host entry of individual viruses and follow viral translation and replication in single cells. Surprisingly, we observe a large degree of heterogeneity in viral infection dynamics in different cells, with viruses rapidly replicating to high numbers in some cells, while showing no replication at all in other cells. A similar heterogeneity is observed in the host response to the infection, which is critical to fight off the virus. We are employing VIRIM to uncover the mechanisms underlying heterogeneity in infection and are trying to understand how viral and host gene expression is coordinated to optimize viral replication and anti-viral signaling, respectively. Together, these studies can serve as a starting point for the development of new targeted therapies against virus infections.

Key publications

Long-term imaging of individual ribosomes reveals ribosome cooperativity in mRNA translation

Madern MF*, Yang S*, Witteveen O, [...] Tanenbaum ME

Cell

Download|2025

Antiviral responses are shaped by heterogeneity in viral replication dynamics

Bruurs LJM, Müller M, [...] van Kuppeveld F, Tanenbaum ME

Nature microbiology 8(11):2115–2129

Download|2023

Translation and Replication Dynamics of Single RNA Viruses

Boersma S, Rabouw HH, Bruurs LJM, [...] van Kuppeveld F*, Tanenbaum ME*

Cell: 183, 1–16

Download|2020

Single-molecule imaging uncovers rules governing nonsense-mediated mRNA decay

Hoek TA*, Khuperkar D*, Lindeboom RGH, [...] Tanenbaum ME

Molecular Cell 75(2):324-339

Download|2019

Multi-color single-molecule imaging uncovers extensive heterogeneity in mRNA decoding

Boersma S*, Khuperkar D*, Verhagen BMP, [...] Tanenbaum ME

Cell 178(2):458-472

Download|2019

Dynamics of translation of single mRNA molecules in vivo.

Yan X, Hoek TA, Vale RD and Tanenbaum ME.

Cell; 165(4):976-89

Download|2016

Other publications

Zero-Mode Waveguide Nanowells for Single-Molecule Detection in Living Cells

Yang S*, Klughammer N*, Barth A*, [...] Tanenbaum ME#, Dekker C#

ACS Nano 17(20):20179-20193

Download|2023

Time-resolved single-cell sequencing identifies multiple waves of mRNA decay during the mitosis-to-G1 phase transition

Krenning L, Sonneveld S, [...] Tanenbaum ME

eLife 11:71356

Download|2022

A public-private partnership model for COVID-19 diagnostics

Krijger PHL*, Hoek TA*, [...] de Laat W#, Tanenbaum ME#

Nat Biotechnol. 39(10):1182-1184

Download|2021

mRNA structural dynamics shape Argonaute-target interactions

Ruijtenberg S*, Sonneveld S*, Cui TJ, [...] Tanenbaum ME

Nat Struct Mol Biol. 28(6):533

Download|2020

Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent

Jost M, Chen Y, [...] Tanenbaum ME*, Weissman JS*

Mol Cell. 79(1):191-198

Download|2020

Quantification of mRNA translation in live cells using single-molecule imaging

Khuperkar D*, Hoek TA*, Sonneveld S, [...] Tanenbaum ME

Nat Protoc. 15(4):1371–1398

Download|2020

Group leader

Marvin Tanenbaum

Marvin Tanenbaum is senior group leader at the Hubrecht Institute, Investigator at Oncode Institute and Professor in the department of Bionanoscience at the TU Delft. His group studies the molecular mechanisms of gene expression control at the single-molecule level, both for humans and in viruses, and aims to understand how control of gene expression affects important cellular decisions. The Tanenbaum group has developed several new techniques, including the SunTag fluorescence imaging system. They are using the SunTag system to visualize and quantify regulation of single mRNA molecules in living cells to study the dynamics and regulation of each individual mRNA in time and space. Adaptation of the SunTag imaging system to RNA viruses has enabled live observation of viral infection and gene expression regulation, which is uncovering exciting new mechanisms in viral infection and host response to replicating viruses. In addition to his research activities, Marvin has also co-developed a major new medical diagnostics platform which was widely used during the SARS-CoV-2 pandemic. Marvin also leads a new initiative at the Hubrecht Institute, the Hubrecht Talent Program (HTP), that aims to support minority students in science (see https://www.hubrecht.eu/about-us/hubrecht-talent-program/).

Scientific training and positions

Awards

Group members

Marvin Tanenbaum

Group Leader

Leonie Apperloo

Technician

Huib Rabouw

Postdoc

Dhanushika Ratnayake

Postdoc

Sora Yang

Postdoc

Bernhard Kramer

Postdoc

Thomas Sabate

Postdoc

Bram Verhagen

PhD Student

Max Madern

PhD Student

Micha Müller

PhD Student

Marloes van Drimmelen

PhD Student

Janin Schokolowski

PhD Student

Jakob Puschel

PhD Student

Matthijs Baars

Researcher

Show all group members

Lucas Bruurs	Postdoc 2018-2024	Current: Senior Scientist, Bilthoven Biologicals
Jet Segeren	Postdoc 2022-2024	Current: Science Liaison Fundamental Research, KWF
Rupa Banerjee	Postdoc 2018-2023	Current: Research Scientist, Lemba Therapeutics
Ive Logister	Lab Manager / Research Technician 2016-2022	Current: Principle Research Associate, Genmab
Sanne Boersma	PhD student 2016-2021	Current: Postdoc, Oyler-Yaniv lab, Harvard Medical School
Stijn Sonneveld	PhD student 2016-2021	Current: Data Analist at Nationale-Nederlanden by Working Talent
Tim Hoek	PhD student 2015-2021	Current: Scientist, Screening & Assay Technologies, Genmab
Deepak Khuperkar	Postdoc 2016-2020	Current: Postdoc, King’s College London & Cambridge University
Suzan Ruijtenberg	Postdoc 2015-2019	Current: Assistant professor, University Utrecht
Lenno Krenning	Postdoc 2016-2018	Current: Senior Scientist, Crown Bioscience

Single-molecule analysis of gene expression in living cells

Visualizing translation, transcription and replication of single RNA viruses

Key publications

Other publications

Group leader

Marvin Tanenbaum

Group members

Marvin Tanenbaum

Leonie Apperloo

Huib Rabouw

Dhanushika Ratnayake

Sora Yang

Bernhard Kramer

Thomas Sabate

Bram Verhagen

Max Madern

Micha Müller

Marloes van Drimmelen

Janin Schokolowski

Jakob Puschel

Matthijs Baars

Lab alumni

Open positions

Open positions for Master Students

Tools and reagents

Videos

Single molecule tracking of single kinesin motors using the SunTag

Real-time visualization of translation of single mRNA molecules

Virus infection real-time imaging (VIRIM). Viral replication

Ribosomes translating socRNA

Single influenza A virus entering a host cell