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.
Press Releases and Highlights
(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
(2019) Mechanism-Dependent Modulation of Ultrafast Interfacial Water Dynamics in Intrinsically Disordered Protein Complexes, Angewandte Chemie International Edition 58(14), p. 4720-4724, John Wiley & Sons, Ltd, url, doi:10.1002/ANIE.201813354
(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
(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
(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
(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