Dr. Suzan Ruijtenberg
We are a young research group where we focus on how translational regulation contributes to cellular behavior and developmental decisions, using a combination of genetic, biochemical and single molecule imaging approaches. In addition, we aim to develop new, innovative imaging and labeling technologies which allow us to visualize and control gene expression dynamics.
Our human body consists of trillions of cells, which together form our tissues and organs. The behavior, identity and functioning of each of these cells depends on the proteins present in the cell. Accurate protein levels are of critical importance as even small deviations in the levels of a single protein can have a big impact on cellular function and can lead to diseases. Often mRNA levels are used as a proxy for protein levels. However, recent advances in genome wide technologies have revealed that mRNA levels by themselves are not sufficient to predict protein abundance as translation rates between different mRNAs or between the same mRNA within a different cellular environment can vary substantially. Particularly during dynamic processes, such as developmental transitions and cellular differentiation, translational control is likely to have an important role in gene expression.
The goal of the group is to visualize and understand when and where proteins are synthesized and how changes in translation efficiencies affect cell fate and organismal behavior.
To address these questions, we will make use of the round worm Caenorhabditis elegans (C. elegans) as a model system. C. elegans provides an attractive animal system in which to study the role of translational control during development for several reasons. Most importantly, the animal is fully transparent, which allows us to visualize translation in all the different cell types as they differentiate and the animal grows. In addition, most of the proteins involved in translation (including translation initiation, elongation and termination factors, as well as the ribosomal proteins) are conserved between worms and humans. Moreover, its invariant cell linage and the wide variety of efficient genetic tools, make C. elegans a very attractive animal to study the dynamics of translation and identify new regulators of translation.
Ruijtenberg S, Hoek TA, Yan X, Tanenbaum ME. Imaging Translation Dynamics of Single mRNA Molecules in Live Cells. RNA Detection. Methods in Molecular Biology, vol 1649 2018
van Rijnberk LM, van der Horst SE, van den Heuvel S, Ruijtenberg S. A dual transcriptional reporter and CDK-activity sensor marks cell cycle entry and progression in C. elegans. PLoS ONE 2017 Feb 12(2)
Ruijtenberg S, van den Heuvel S. Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. Cell Cycle. 2016 Jan 17;15(2):196-212.
Ruijtenberg S, van den Heuvel S. G1/S Inhibitors and the SWI/SNF Complex Control Cell-Cycle Exit during Muscle Differentiation. Cell. 2015 Jul 16;162(2):300-13.
The I, Ruijtenberg S, Bouchet BP, Cristobal A, Prinsen MB, van Mourik T, Koreth J, Xu H, Heck AJ, Akhmanova A, Cuppen E, Boxem M, Muñoz J, van den Heuvel S. Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells. Nat. Commun. 2015 Jan 6;6:5906.
Korzelius J, The I, Ruijtenberg S, Prinsen MB, Portegijs V, Middelkoop TC, Groot Koerkamp MJ, Holstege FC, Boxem M, van den Heuvel S. Caenorhabditis elegans cyclin D/CDK4 and cyclin E/CDK2 induce distinct cell cycle re-entry programs in differentiated muscle cells. PLoS Genet. 2011 Nov;7(11)
Ruijtenberg S, van den Heuvel S, The I. Regulation of DNA synthesis and replication checkpoint activation during C. elegans development. InTech Open Access Books. Edited by Jelena Kusic-Tisma. 2011 Sep. ISBN 978-953-307-775-8
Korzelius J, The I, Ruijtenberg S, Portegijs V, Xu H, Horvitz HR, van den Heuvel S. C. elegans MCM-4 is a general DNA replication and checkpoint component with an epidermis-specific requirement for growth and viability. Dev. Biol. 2011 Feb 15;350(2):358-69.