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The Tanenbaum group uses cutting-edge live-cell single molecule microscopy and new types of genetic engineering to study the molecular mechanisms of gene expression control in individual cells.
We aim to understand how regulation of gene expression affects important cell fate decisions. In addition, we are constantly developing and applying new imaging technologies to visualize gene expression dynamics with ever increasing resolution.
We have recently developed a new 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 much 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 technology, we can now continuously monitor translation of individual mRNA molecules in space and time (Fig. 1B; Yan et al., 2016, Cell).
We are employing SunTag technology to visualize gene expression control in living cells with incredible precision to uncover how regulatory mechanisms function at the molecular level, and how regulation of protein expression affects cell fate decisions. 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.
Control of gene expression is critical for cell fate and homeostasis, and is often de-regulated in diseases like cancer. To study the function of gene expression regulation, it is critical to be able to perturb it. However, modulating the expression of endogenous genes has been very challenging. Recently, in collaboration with the lab of Jonathan Weissman at UCSF, we have developed a new system to modulate transcription rates of endogenous genes. In this system, a nuclease-dead CRISPR/Cas9 protein is fused to transcription activation domains through the SunTag and targeted to an endogenous gene promotor to modulate transcription (Fig. 2) (Tanenbaum et al., 2014, Cell).
We are using this new technology to study how transcriptional regulation drives key cell cycle transitions, and how transcriptional control interplays with other gene expression regulatory mechanisms, like mRNA stability and translation.
Hundreds of proteins show altered expression as cells progress through the cell cycle, but the mechanisms underlying these changes remain poorly understood. While a significant body of work has focused on regulation of protein degradation, very little is known about the control of protein synthesis, even though protein levels are equally dependent on protein degradation and synthesis. Protein synthesis rates can be regulated through many different regulatory mechanisms, including transcriptional and translational control, mRNA localization and mRNA stability. We have developed new techniques to visualize different steps of gene expression in single cells to understand how the different mechanisms that alter gene expression activity are controlled as cells progress through the cell cycle (Tanenbaum et al., 2015, eLife). Using these techniques, we aim to understand how protein levels are modulated over time and how control of gene expression ensures reliable cell cycle decisions in single cells.
Jost M, Chen Y*, Gilbert LA*, Horlbeck MA*, Krenning L*, Menchon G*, Rai A*, Cho MY, Stern JJ, Prota AE, Kampmann M, Akhmanova A, Steinmetz MO, Tanenbaum ME# and Weissman JS#.
# Corresponding authors
Yan X, Hoek TA, Vale RD and Tanenbaum ME.
Tanenbaum ME, Stern-Ginossar N, Weissman JS and Vale RD.
McKenney RJ, Huynh W, Tanenbaum ME, Bhabha G and Vale RD.
Tanenbaum ME, Gilbert LA, Qi LS, Weissman JS and Vale RD.
Tanenbaum ME*, Vale RD and McKenney RJ*.
Marvin Tanenbaum is group leader at the Hubrecht Institute. His group studies the molecular mechanisms of gene expression control at the single cell level 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. Using the SunTag system they can directly visualize and quantify translation of single mRNA molecules in living cells to study the dynamics and regulation of each individual mRNA in real time. In addition, the SunTag was re-purposed to create an artificial transcription factor to precisely modulate gene expression of endogenous genes.
Scientific training and positions
MSc Student 2016
BSc Student 2017
Dion de Steenwinkel
MSc Student 2016-2017
We are currently interested in recruiting enthusiastic, motivated people that are interested in working in a highly ambitious, multidisciplinary team. We are interested in applicants from a variety of backgrounds, including Biophysics, Cell Biology, Biochemistry and Computational biology. We have several projects available involving real-time imaging of gene expression dynamics.
If you are interested in learning more about the available position(s) in the lab, please send an email to Marvin Tanenbaum, including a CV (with grades), a coverletter and names and contact information of 3 references.
We have several exciting projects involving a variety of topics and techniques available for Master students. Please email Marvin Tanenbaum if you are interested in a internship/rotation in the lab. We welcome students from both life sciences and physical sciences.
Utrecht Science Park