Simon Elsässer

Karolinska Institutet

External website

simon.elsasser@ki.se

Keywords

Chemical biology, chromatin, Epigenetics, Next-gen sequencing, Stem Cells, synthetic biology

Key publications

Chromatin Biology

Navarro, C., Lyu, J., Katsori, A.-M., Caridha, R., & Elsässer, S. J. (2020).
An embryonic stem cell-specific heterochromatin state promotes core histone exchange in the absence of DNA accessibility.
Nature Communications, 11(1), 5095. https://doi.org/10.1038/s41467-020-18863-1

Kumar, B., & Elsässer, S. (2019).
Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells.
Cell Reports. https://doi.org/10.1101/557082

Elsässer, S. J., Ernst, R. J., Walker, O. S., & Chin, J. W. (2016).
Genetic code expansion in stable cell lines enables encoded chromatin modification.
Nature Methods, 13(2), 158–164. https://doi.org/10.1038/nmeth.3701

Elsässer, S. J., Noh, K. M., Diaz, N., Allis, C. D., & Banaszynski, L. A. (2015).
Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells.
Nature. https://doi.org/10.1038/nature14345

Microproteins

Lafranchi, L., Schlesinger, D., Kimler, K. J., & Elsässer, S. J. (2020).
Universal Single-Residue Terminal Labels for Fluorescent Live Cell Imaging of Microproteins.
Journal of the American Chemical Society, jacs.0c09574. https://doi.org/10.1021/jacs.0c09574

Synthetic Biology

Meineke, B., Heimgärtner, J., Eirich, J., Landreh, M., & Elsässer, S. J. (2020).
Site-Specific Incorporation of Two ncAAs for Two-Color Bioorthogonal Labeling and Crosslinking of Proteins on Live Mammalian Cells.
Cell Reports, 31(12), 107811. https://doi.org/10.1016/j.celrep.2020.107811

van Husen, L. S., Schedin-Weiss, S., Trung, M. N., Kazmi, M. A., Winblad, B., Sakmar, T. P., Elsässer, S. J., & Tjernberg, L. O. (2019).
Dual Bioorthogonal Labeling of the Amyloid-β Protein Precursor Facilitates Simultaneous Visualization of the Protein and Its Cleavage Products.
Journal of Alzheimer’s Disease, 72(2), 537–548. https://doi.org/10.3233/JAD-190898

Elsässer, S. J. (2018).
Generation of Stable Amber Suppression Cell Lines.
Methods in Molecular Biology (pp. 237–245). https://doi.org/10.1007/978-1-4939-7574-7_15

Meineke, B., Heimgärtner, J., Lafranchi, L., & Elsässer, S. J. (2018).
Methanomethylophilus alvus Mx1201 Provides Basis for Mutual Orthogonal Pyrrolysyl tRNA/Aminoacyl-tRNA Synthetase Pairs in Mammalian Cells.
ACS Chemical Biology, 13(11), 3087–3096. https://doi.org/10.1021/acschembio.8b00571

Science Policy

Pesic, M., Egamberdieva, D., Kolodziejczyk, B., Elsässer, S. J., Neergheen, V. S., & Kagansky, A. (2020).
Towards policies that capture the expected value of biomolecular diversity for drug discovery, human health, and well-being.
Biologia Futura. https://doi.org/10.1007/s42977-020-00043-3

Neergheen-Bhujun, V., Awan, A. T., Baran, Y., Bunnefeld, N., Chan, K., dela Cruz, T. E., Egamberdieva, D., Elsässer, S., Johnson, M. V., Komai, S., Konevega, A. L., Malone, J. H., Mason, P., Nguon, R., Piper, R., Shrestha, U. B., Pešić, M., & Kagansky, A. (2017).
Biodiversity, drug discovery, and the future of global health: Introducing the biodiversity to biomedicine consortium, a call to action.
Journal of Global Health, 7(2). https://doi.org/10.7189/jogh.07.020304

SciLifeLab / Contact / Simon Elsässer

Fellow, Science for Life Laboratory
Fellow, Ming Wai Lau Center of Reparative Medicine
Department of Medical Biochemistry and Biophysics
Karolinska Institutet

Research Interests

Proteins perform a myriad of functions in every living cell. Traditional biochemical approaches for elucidating molecular mechanism rely on a reductionist’s approach of simplifying complex systems into biochemically tractable problems. However, some of the most intriguing problems of biology, for example how the eukaryotic genome is packaged in the nucleus in such way that the relevant information for any given cell state can be made available ‘on demand’, can ultimately only be answered in the context of the full complexity of the living cell. We are exploring solutions to answer my biochemical questions in the context of the living cell. Methodology that would allow such strategy would need to provide a means for: 1) selectively addressing(i.e. manipulate and/or observe) a specific protein of interest in the context of the entire protein complement. 2) precisely synchronizing the biochemical process to be studied within an entire population of cells, so that meaningful biochemical and ’omics’ readouts can be made from the cell population. Synthetic building blocks in form of non-canonical amino acids(ncAAs), introduced into the protein of interest, provide such means for performing biochemistry in the living cell. My laboratory currently focuses on a number of areas:

Development of mammalian ncAA technology for studying proteins in situ, as well as for protein engineering
Quantitative ChIP-Seq for studying dynamic evolution of chromatin states (also using ncAA technology) in the context of pluripotency and lineage commitment
The small proteome (peptidome) of mammalian cells, in particular in the context of pluripotency and lineage commitment
Elucidating the role of unusual DNA structures such as G4 quadruplexes, DNA/RNA hybrids and ssDNA through development of genome-wide profiling methods

Group members

Angelo Salazar (PhD Student)
Anna-Maria Katsori (Postdoc)
Banushree Kumar (PhD Student)
Birthe Meineke (Postdoc)
Carmen Navarro (Postdoc)
Dörte Schlesinger (PhD Student)
Jing Lyu (PhD Student)
Johannes Heimgartner (Master Student)
Jurgen Eirich (Postdoc)
Lorenzo Lafranchi (Postdoc)
Philip Yung (Postdoc)
Rozina Caridha (Lab Manager)
Rui Shao (PhD Student)