Systematic mapping of epigenetic marks to the 3D architecture of the human genome in single cells

Ellenberg and Jungmann will take an interdisciplinary approach combining chemical biology and biophysics to develop a novel technology to use barcoded fluorescent proteins to “paint” DNA sequences with specific epigenetic marks, and super-resolution microscopy to visualize those painted sequences at the level of single genes. With this tool, they will be able to map the complete 3D architecture of the epigenome in single human cells, and analyze how the structure changes during gene activation and repression.

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Affiliated Investigators

Jan Ellenberg, Ph.D.

European Molecular Biology Laboratory

Jan Ellenberg is Head of the Cell Biology & Biophysics Unit and senior scientist at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. He graduated with a degree in biology from the University of Hamburg and obtained his PhD in biochemistry from the Free University of Berlin, during which time he trained primarily at the National Institutes of Health (NIH). In 1999 he started his own group at EMBL in the Gene Expression and Cell Biology & Biophysics Unit at EMBL. He subsequently became coordinator of the Gene Expression Unit in 2006 and since 2010 heads the Cell Biology & Biophysics Unit. Over the past 20 years, Jan has been interested in cell division and nuclear organization, including systematic analysis of mitosis, nuclear pore complex structure and assembly, as well as chromatin organization and formation and segregation of mitotic and meiotic chromosomes. His goal has been to obtain structural and functional measures of the required molecular machinery inside cells using quantitative 4D imaging, single molecule spectroscopy, as well as light sheet and super-resolution microscopy, which his group is constantly developing and automating to address all molecular components comprehensively. His research group played a key role in large EU-wide efforts on systems biology of mitosis, as well as microscopy automation and unbiased computational image analysis, (www.mitocheck.org, www.mitosys.org, www.systemsmicroscopy.eu), establishing methods to reliably score up to billions of cells and capture rare and transient functional states automatically. He is a member of several editorial, as well as scientific advisory boards of renowned international journals and research institutes. Due to the important role of new imaging technologies for the future life sciences, he has coordinated European efforts to make imaging technologies more accessible to researchers as open access research infrastructures, which he promotes in his role as as EMBL delegate in the EurobioImaging Interim Board and Coordinator of the Euro-BioImaging Preparatory Phase (www.eurobioimaging.eu). For his scientific merits within cell biology plus his engagement in the integration of bio sciences he was conferred to honorary doctor of philosophy at the Åbo Akademi University, Turku, Finland in 2016.

Ralf Jungmann, Ph.D.

Max Planck Institute of Biochemistry and LMU Munich

In his research, Ralf Jungmann combines single-molecule super-resolution microscopy with DNA nanotechnology to enable novel applications in cell biology and biomedicine.

Using the unique programmability of DNA molecules, he pushes the envelope in microscopy technique development to eventually perform highly multiplexed (hundreds of targets), ultra-resolution (<5 nm), and quantitative (integer counting of molecules) imaging of biomolecules (i.e. proteins and nucleic acids) and their interactions.

His vision is to unravel the location and interplay of a multitude of genes, RNAs, and proteins in a truly quantitative fashion with highest spatial resolution in single cells.

Ralf Jungmann studied Physics at Saarland University, followed by a one-year diploma research stay with Paul Hansma at UC Santa Barbara where he worked on functional imaging of bone ultrastructure using Atomic Force Microscopy and High-Speed-Photography. In 2007, Jungmann joined Friedrich Simmel’s lab at TU Munich as a Ph.D. student and was among the first researchers in Germany to use and advance the DNA origami technique. During his Ph.D., Jungmann applied single-molecule fluorescence techniques to DNA Nanotechnology, constructing the first nanoscopic DNA origami “rulers” for super-resolution microscopy. He also pioneered DNA-PAINT, a super-resolution method that uses programmable DNA molecules as imaging probes. After receiving his Ph.D. at TUM, he moved to the labs of Peng Yin and William Shih at the Wyss Institute for Biologically Inspired Engineering at Harvard University as an Alexander von Humboldt fellow. At Harvard, Jungmann worked on applications of DNA-PAINT for multiplexed cellular imaging.

In 2014, Jungmann received an Emmy Noether Fellowship from the German Research Foundation (DFG) and since then heads the research group “Molecular Imaging and Bionanotechnology” at the MPI of Biochemistry and the LMU Munich. In 2015, Jungmann co-founded Ultivue, a US-based company commercializing multiplexed DNA-based imaging for digital pathology.

In 2016 he received an ERC Starting Grant to bring DNA-based super-resolution imaging from single molecules to whole cells and tissues. Since August 2016, he is Professor of Physics at the LMU Munich. 

In 2017, Jungmann became Allen Distinguished Investigator in Epigenetics. He is exploring ways to visualizes genome-wide epigenetic marks and gene locations in a joint project with Jan Ellenberg from the EMBL. 

In 2018, Jungmann was awarded an HFSP Young Investigator Award together with Maartje Bastings from Switzerland and Ian Parish from Australia to create synthetic DNA origami-based T-Cell receptors and apply multiplexed super-resolution microscopy in immunology.