Embryonic stem (ES) cells are derived from the inner cell mass of the embryo at the blastocyst stage. They can be maintained in culture and instructed to differentiate towards virtually any cell type of the body, thereby providing a powerful tool to study developmental processes in vitro. In addition, they are a promising source for future cell therapy applications, which aim at replacing cells lost in pathological conditions such as Parkinson’s disease, myocardial infarction, diabetes, and other major human diseases.
We use ES cells as a model system to understand to quantitatively characterize how temporal fluctuations and intercellular variability in different steps of gene expression shapes protein levels in cell populations, and how this impact cell fate decisions. Our second line of research focuses on cell cycle gating of transcription factor activity and how these search the genome for their specific binding sites.
The expertise of our laboratory lies mainly in molecular and cell biology, with a strong emphasis on quantitative time-lapse imaging. We are also very interested in biophysical and computational modeling approaches, which we use mainly through collaborations with local or external groups.
Selected recent publications from our laboratory
Phillips NE*, Mandic A*, Omidi S, Naef F†, Suter DM†. Memory and relatedness of transcriptional activity in mammalian cell lineages. *,†Equal contribution. Nature Communications 2019 March 14
Here we show how variability in transcriptional activity propagates through cell lineages. We found that gene expression memory scales with transcriptional variability, in other words genes that are “noisy” at the population level display longer transcriptional memory.
Alber AB*, Paquet ER*, Biserni M, Naef F, Suter DM. Single Live Cell Monitoring of Protein Turnover Reveals Intercellular Variability and Cell-Cycle Dependence of Degradation Rates. Molecular Cell 2018 Aug 23.
We developed a new method allowing to measure both protein synthesis and degradation rates simultaneously in single living cells. This allowed us to understand how these two parameters interplay to regulate protein accumulation over the cell cycle, and led to the surprising finding that cells vary broadly in their global protein degradation rates but compensate this variability by adjusting their protein synthesis rates.
Deluz C*, Friman ET*, Strebinger D*, Benke A, Raccaud M, Callegari A, Leleu M, Manley S, Suter DM. A role for mitotic bookmarking of SOX2 in pluripotency and differentiation. Genes & Development 2016 Dec 5.
Here we show that the transcription factor SOX2 associates with mitotic chromosomes, and that its depletion at the mitosis-G1 transition impairs its function in regulating self-renewal and differentiation of ES cells. This was the first demonstration of the role of a transcription factor at the mitosis-G1 transition in cell fate determination.
Earlier selected publications
Molina N*, Suter DM*†, Zoller B, Gotic I, Naef F†. Stimulus-induced modulation of transcriptional bursting in a single mammalian gene. *Equal contribution; †Corresponding authors. PNAS, 2013 Dec 17
Gebhardt JCM* Suter DM*, Roy R, Zhao ZW, Chapman A, Basu S, Maniatis T, Xie XS. Probing Transcription Factor DNA Binding at the Single Molecule Level in Live Mammalian Cells. *Equal contribution. Nature Methods, 2013 Aug;10(8):692
Stratmann M*, Suter DM*, Molina N, Naef F, Schibler U. Circadian Dbp Transcription Relies on Highly Dynamic BMAL1-CLOCK Interaction with E Boxes and Requires the Proteasome. *Equal contribution. Molecular Cell. 2012 Oct 26
Suter DM*, Molina N*, Gatfield D, Schneider K, Schibler U, Naef F. Mammalian genes are transcribed with widely different bursting kinetics. *Equal contribution. Science. 2011 Apr 22