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We focus on studying intrinsically disordered proteins (IDPs), which constitute up to 50% of the eukaryotic proteome. IDPs are most infamous for their role in neurodegenerative aging deaseases, like huntington, parkison, alzheimer etc. However, IDPs are actually central in many vital biological processes, such as nucleocytoplasmic transport, transcription and gene regulation. The ability of IDPs to exist in multiple conformations is considered a major driving force behind their enrichment during evolution in eukaryotes. Studying biological machineries containing such dynamic proteins is a major hurdle for conventional technologies. Because of this and as they are hard to visualize, IDPs are termed the dark proteome. Using a question-driven, multidisciplinary approach paired with novel tool development, we have made major strides in understanding the biological dynamics of such systems from the single molecule to the whole cell level.

Fluorescence tools are ideally suited to study the plasticity of IDPs, since their non-invasive character permits smooth transition between in vitro (biochemical) and in vivo (in cell) studies. In particular, single molecule and superresolution techniques are powerful tools for studying spatial and temporal heterogeneities that are intrinsic to complex biological systems. We synergistically combine this effort with advanced tool developments in synthetic biology, chemical biology, microfluidics and microscope engineering to increase the throughput, strength and sensitivity of the approach as a whole.

10 most significant publications of the past 10 years

You can find an overview over all publications on pubmed.
ORCID: 0000-0002-0634-0503

Miao Yu, Maziar Heidari, Sofya Mikhaleva, Piau Siong Tan, Sara Mingu, Hao Ruan, Christopher D Reinkemeier, Agnieszka Obarska-Kosinska, Marc Siggel, Martin Beck, Gerhard Hummer, Edward A Lemke (2023) Visualizing the disordered nuclear transport machinery in situ, | Nature | 617, url, doi:10.1038/s41586-023-05990-0

Christopher D. Reinkemeier, Edward A. Lemke (2021) Dual film-like organelles enable spatial separation of orthogonal eukaryotic translation, Cell 184(19), p. 4886-4903.e21, Cell Press, doi:10.1016/J.CELL.2021.08.001

Giorgia Celetti, Giulia Paci, Joana Caria, Virginia VanDelinder, George Bachand, Edward A. Lemke (2020) The liquid state of FG-nucleoporins mimics permeability barrier properties of nuclear pore complexes, The Journal of cell biology 219(1), J Cell Biol, url, doi:10.1083/JCB.201907157

Christopher D. Reinkemeier, Gemma Estrada Girona, Edward A. Lemke (2019) Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes, Science 363(6434), American Association for the Advancement of Science, url, doi:10.1126/SCIENCE.AAW2644/SUPPL_FILE/AAW2644S1.MP4

Gustavo Fuertes, Niccolò Banterle, Kiersten M. Ruff, Aritra Chowdhury, Davide Mercadante, Christine Koehler, Michael Kachala, Gemma Estrada Girona, Sigrid Milles, Ankur Mishra, Patrick R. Onck, Frauke Gräter, Santiago Esteban-Martín, Rohit V. Pappu, Dmitri I. Svergun, Edward A. Lemke (2017) Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS vs. FRET measurements, Proceedings of the National Academy of Sciences of the United States of America 114(31), p. E6342-E6351, National Academy of Sciences, url, doi:10.1073/PNAS.1704692114/-/DCSUPPLEMENTAL

Christine Koehler, Paul F. Sauter, Mirella Wawryszyn, Gemma Estrada Girona, Kapil Gupta, Jonathan J.M. Landry, Markus Hsi Yang Fritz, Ksenija Radic, Jan Erik Hoffmann, Zhuo A. Chen, Juan Zou, Piau Siong Tan, Bence Galik, Sini Junttila, Peggy Stolt-Bergner, Giancarlo Pruneri, Attila Gyenesei, Carsten Schultz, Moritz Bosse Biskup, Hueseyin Besir, Vladimir Benes, Juri Rappsilber, Martin Jechlinger, Jan O. Korbel, Imre Berger, Stefan Braese, Edward A. Lemke (2016) Genetic code expansion for multiprotein complex engineering, Nature Methods 2016 13:12 13(12), p. 997-1000, Nature Publishing Group, url, doi:10.1038/nmeth.4032

Ivana Nikić, Gemma Estrada Girona, Jun Hee Kang, Giulia Paci, Sofya Mikhaleva, Christine Koehler, Nataliia V. Shymanska, Camilla Ventura Santos, Daniel Spitz, Edward A. Lemke (2016) Debugging Eukaryotic Genetic Code Expansion for Site-Specific Click-PAINT Super-Resolution Microscopy, Angewandte Chemie (International ed. in English) 55(52), p. 16172-16176, Angew Chem Int Ed Engl, url, doi:10.1002/ANIE.201608284

Sigrid Milles, Davide Mercadante, Iker Valle Aramburu, Malene Ringkjøbing Jensen, Niccolò Banterle, Christine Koehler, Swati Tyagi, Jane Clarke, Sarah L. Shammas, Martin Blackledge, Frauke Gräter, Edward A. Lemke (2015) Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors, Cell 163(3), p. 734-745, Cell, url, doi:10.1016/J.CELL.2015.09.047

Ivana Nikic̈, Tilman Plass, Oliver Schraidt, Jȩdrzej Szymański, John A.G. Briggs, Carsten Schultz, Edward A. Lemke (2014) Minimal tags for rapid dual-color live-cell labeling and super-resolution microscopy, Angewandte Chemie (International ed. in English) 53(8), p. 2245-2249, Angew Chem Int Ed Engl, url, doi:10.1002/ANIE.201309847

Swati Tyagi, Virginia Vandelinder, Niccolò Banterle, Gustavo Fuertes, Sigrid Milles, Morgane Agez, Edward A. Lemke (2014) Continuous throughput and long-term observation of single-molecule FRET without immobilization, Nature Methods 2014 11:3 11(3), p. 297-300, Nature Publishing Group, url, doi:10.1038/nmeth.2809

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We are a multidisciplinary group of chemists, physicists, biologists and engineers interested in understanding molecular mechanisms that are driven by disorder.