We are a multidisciplinary group of chemists, physicists, biologists and engineers interested in understanding molecular mechanisms that are driven by disorder. We develop biophysical tools to visualize molecular mechanisms in vitro and in cells with the highest combined temporal and spatial resolution and we innovate synthetic biology approaches to tune, control and study molecular and cellular processes.
We focus on studying intrinsically disordered proteins (IDPs), which constitute up to 50% of the eukaryotic proteome. IDPs are found 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.
here you can see the most significant publications in the past 10 years
please find more on PubMed.gov
- Reinkemeier CD, Estrada Girona G, Lemke EA*, (2019) Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes. Science, http://dx.doi .org/10.1126/science.aaw2644
- Fuertes G, BanterleN, Ruff K, Chowdhury K, Mercadante D, Koehler C, Kachala M, Estrada Girona G, Milles S, Mishra A, Onck P, Gräter F, Esteban-Martín S, Pappu R*, Svergun D*, Lemke EA*. 2017 Decoupling of size and shape fluctuations in heteropolymeric sequences reconciles discrepancies in SAXS versus FRET measurements,. Proc Natl Acad Sci USA. Aug 1;114(31):E6342-E6351
- Nikić I, Estrada Girona G, Kang JH, Paci G, Mikhaleva S, Koehler C, Shymanska NV, Ventura Santos C, Spitz D, Lemke EA*. 2016. Debugging eukaryotic genetic code expansion for site-specific click-PAINT super-resolution microscopy. Angew Chem Int Ed Engl. 55(52):16172-16176
- Koehler C, Sauter PF, Wawryszyn M, Estrada Girona G, Gupta K, Landry JJM, Hsi‐Yang Fritz M, Radic K, Hoffmann J-E, Chen ZA, Zou J, Tan PS, Galik B, Junttila S, Stolt‐Bergner P, Pruneri G, Gyenesei A, Schultz C, Biskup MB, Besir H, Benes V, Rappsilber J, Jechlinger M, Korbel JO, Berger I, Braese S, Lemke EA*. 2016. Genetic code expansion for multiprotein complex engineering, Nature Methods. (12):997-1000
- Milles S, Mercadante D, Aramburu IV, Jensen MR, Banterle B, Koehler C, Tyagi S, Clarke J, Shammas S, Blackledge M*, Gräter F*, Lemke EA*. 2015. Plasticity of an ultrafast interaction between nucleoporin and transport receptors, Cell. 163(3):734-45
- Milles S, Lemke EA*. 2014. Mapping multivalency and differential affinities within large intrinsically disordered protein complexes with segmental motion analysis. Angew Chem Int Ed Engl. 53(28):7364-7367
- Tyagi S, VanDelinder V, Banterle N, Fuertes G, Milles S, Agez M, Lemke EA*. 2014. Continuous throughput and long-term observation of single-molecule FRET without immobilization. Nature Methods. (3):297-300
- Nikic I, Plass T, Schraidt O, Szymanski J, Briggs JA, Schultz C, Lemke EA*. 2014. Minimal tags for rapid dual-color live-cell labeling and super-resolution microscopy. Angew Chem Int Ed Engl. (8), 2245-2249
- Plass T, Milles S, Koehler C, Szymanski J. Mueller R, Wieβler M, Schultz C*, Lemke EA*. 2012. Amino Acids for Diels-Alder Reactions in Living Cells. Angew Chem Int Ed Engl. 23;51(17):4166-70
- Plass T, Milles S, Koehler C, Schultz C*, Lemke EA*. 2011. Genetically encoded copper-free click chemistry. Angew Chem Int Ed Engl. 18;50 (17):3878-3881