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The Biophysics Division at the Department of Biology of the University of Osnabrück promotes research and teaching in molecular and cellular biophysics. Our mission is to bridge the gap between the biological and the physicochemical perspective on cellular processes. To this end we have developed a broad spectrum of biophysical tools for quantifying molecular functions in complex environment, often in the context of lipid membranes. We apply these tools for unraveling the mechanistic determinants of signal transduction across the plasma membrane and we share them in numerous collaborations at the Department of Biology and beyond. Within several Bachelor and Master Courses, we introduce the inherently interdisciplinary concepts of biophysics, which we believe are pivotal for fundamental progress in the understanding of life.

 Signal Transduction Across Biological Membranes

Ligand-induced signal activation via specific receptor proteins in the plasma membrane is a key process for the cell in order to fulfill its complex role within multicellular organisms. While signaling pathways have been mapped in detail, molecular and cellular determinants governing signal propagation across the membrane have remained controversially debated. For cytokine receptors, receptor tyrosine kinases and related receptors, an intricate interplay of lateral interactions and conformational changes induced by the interaction of the ligand to multiple receptor subunits is probably responsible for activating cytosolic effector proteins. Interestingly, a critical role of these processes in regulating signaling specificity is emerging. Our research is focused on developing experimental approaches to quantitatively dissect the molecular and cellular processes involved in receptor assembly and signal activation in the context of the membrane. We tackle this challenge by an interdisciplinary approach based on the following strategies:

Reconstitute signaling complexes on surfaces and in polymer-supported membranes for quantitative interaction studies.

Apply surface-sensitive detections techniques for monitoring protein-protein interactions at interfaces and within lipid membranes.

Unravel the spatiotemporal organization of signaling complexes in the plasma membrane of living cells by single molecule localization microscopy.

Exploit unique properties of nanoparticle as versatile reporter and actuator of molecular functions in living cells.

With a main focus on cytokine receptors, these approaches are used to explore receptor assembly and effector recruitment as well as its regulation by negative feedback regulators. Developing these technologies both profit from and feed into the unique research environment at the University of Osnabrück with its Collaborative Research Center "Physiology and Dynamics of Cellular Microcompartments"(SFB 944) and the interdisciplinary Center of Cellular Nanoanalytics (CellNanOs)

The spatiotemporal organization of cytokine receptor signaling complexes is currently controversially debated. While originally dimerization of two or more receptor subunits by simultaneous interaction with the ligand has been proposed, pre-dimerization and pre-clustering has emerged as an alternative concept. We have devised single molecule fluorescence imaging techniques for quantifying cytokine receptor assembly at the plasma membrane of living cells under close to physiological conditions, i.e. low cell surface receptor expression levels (1).

Binding of fluorescent IFN to endogenous IFNAR in HeLa cells at saturating concentrations.

For this purpose, we have employed posttranslational enzymatic labeling as well as nanobodies for efficient labeling with photostable fluorescence dyes. Using dual-color total internal reflection fluorescence (TIRF) microscopy, direct visualization of diffusion and interaction of the entire population of receptors was achieved in the plasma membrane of living cells (1, 2). Single molecule localization provides unique opportunities for quantitative evaluation of spatial co-organization of receptor subunits.

Single molecule localization-based analyses for quantifying the spatiotemporal receptor organization in the plasma membrane.

Detailed studies on the Type I Interferon (IFN) receptor excluded receptor predimerization or pre-organization in absence of the ligand. However, efficient receptor dimerization was observed upon addition of IFN (1).

Transient dimerization observed in presence IFN furthermore confirmed dynamic equilibrium between binary and ternary complexes.

Transient formation of an individual IFNAR1-IFNAR2 dimer observed by single molecule co-locomotion analysis.

Two-step dimerization of the IFN receptor and formation of a dynamic ternary complex.

Meanwhile, we have confirmed ligand-induced dimerization for several other cytokine receptors including the heterodimeric type II interleukin 4 (IL-4) receptor (2) and the homodimeric erythropoietin (Epo) receptor (3), both members of the class I cytokine receptor family. Surrogate ligands based on receptor-dimerizing diabodies were found to similarly activate signaling (3). These results establish a key role of ligand-induced receptor dimerization for cytokine receptor activation.

  • Relate receptor dimerization and signal activation at the plasma membrane and in endosomes.
  • Unravel the mechanistic role of the associated Janus kinases in the assembly of the signaling complex.
  • Explore the role of lipid environment and plasma membrane microcompartmentalization in receptor assembly and dynamics.
Name Institution State
K. Christopher Garcia Stanford University US
Thomas Müller University of Würzburg Germany
Christophe Lamaze Institut Curie, Paris France
Ian Hitchcock University of York UK
  • Receptor Dimerization Dynamics as a Regulatory Valve for Plasticity of Type I Interferon Signaling (PDF)
    The Journal of Cell Biology 209, Nr. 4 : 579 - 593 (May 2015)
  • Instructive Roles for Cytokine-Receptor Binding Parameters in Determining Signaling and Functional Potency (PDF)
    Science Signaling 8, Nr. 402 (Sep 2015)
  • Tuning Cytokine Receptor Signaling by Re-Orienting Dimer Geometry with Surrogate Ligands (PDF)
    Cell 160, Nr. 6 : 1169 - 1208 (Mar 2015)

Role of USP18 in the dimerization efficiency of IFN variants and mutants with different IFNAR1 binding affinities.

Several cytokine receptors bind different ligands, which can differentially activate cellular responses. The IFN receptor is a paradigm for such receptor plasticity, with 15 different ligands being recognized by a single cell surface receptor. Detailed studies of IFN recognition by its receptor subunits IFNAR1 and IFNAR2 revealed that binding affinity rather than structural differences are responsible for differential IFN activities, suggesting regulation at the level of receptor assembly (1-5). Indeed, systematic tailoring of IFN activities was shown to be possible by engineering its receptor binding affinities (2, 4). Recently, negative feedback regulation by the ubiquitin-specific protease USP18 was found to be a key determinant for differential IFN activity (6). It turned out that USP18 negatively regulates receptor dimerization, probably by binding to the subunit IFNAR2 and thus interfering with possible interactions between the JAKs, as observed by single molecule dimerization experiments (7).

Based on this insight, we have proposed that differential IFN activities are caused by a temporal change in potency, which is determined by a complex interplay of different feedback mechanisms (8, 9).

Feedback mechanisms controlling differential interferon activities, which are characterized by different affinity-potency relationships observed for short-term and long-term cellular responses (8).

  • Unravel the molecular basis of receptor desensitization by USP18.
  • Explore the role of receptor endocytosis and trafficking in regulating signaling specificity.
  • Establish quantitative models for describing differential signaling activities.
Name Institution State
Gideon Schreiber The Weizmann Institute of Science, Rehovot Israel
Gilles Uzé CNRS Montpellier France
K. Christopher Garcia Stanford University US
Christophe Lamaze Institut Curie, Paris France
  • Ligand-induced assembling of the type I interferon receptor on supported lipid bilayers, (PDF)
    J. Mol. Biol. 341 (2004) 303-318.
  • Inquiring into the differential actions of interferons: an IFNalpha2 mutant endowed with enhanced binding affinity to IFNAR1 is functionally similar to IFNbeta, (PDF)
    Mol. Cell. Biol. 26 (2006) 1888-1897.
  • Differential receptor subunit affinities of type I interferons govern differential signal activation, (PDF)
    J. Mol. Biol. 366 (2007) 525-539.
  • The stability of the ternary interferon-receptor complex rather than the affinity to the individual subunits dictates differential biological activities., (PDF)
    J Biol Chem 283, 32925-36.
  • Structural Linkage Between Ligand Discrimination and Receptor Activation by Type I Interferons (PDF)
    Cell 146, Nr. 4 (Aug 2011): 621 - 632
  • USP18-based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon alpha Response (PDF)
    PloS One 6, Nr. 7 (Jul 2011): e22200
  • Structural and Dynamic Determinants of Type I Interferon Receptor Assembly and Their Functional Interpretation (PDF)
    Immunological Reviews 250, Nr. 1 (Nov 2012): 317 - 334
  • The Molecular Basis for Functional Plasticity in Type I Interferon Signaling (PDF)
    Trends in Immunology 36, Nr. 3 : 139 - 149 (Mar 2015)

Tracking of a labeled IFN bound to transmembrane IFNAR2 reconstituted into micropatterned PSM (boundary indicated by the white dashed line).

Reconstitution into polymer-supported membranes (PSM) is a promising approach for studying membrane protein interaction and conformations in a controlled lipid environment by advanced imaging techniques. Based on a dense PEG polymer brush and hydrophobic anchoring groups for capturing protein liposomes, we have developed a robust approach for PSM assembly on glass-type surfaces, which is compatible with single molecule fluorescence imaging, fluorescence correlation spectroscopy and atomic force microscopy (1). Rapid diffusion of a large variety of transmembrane proteins reconstituted into these PSM was found, as well as retained functionality with respect to protein-protein interactions (1, 2).

As the lipid composition can be controlled in these PSM, separation of ld and lo lipid phases is readily achieved (3). Moreover, micropatterned organization of anchoring groups provides unique possibilities to control PSM formation and lipid phase-separation in a spatially resolved manner (3).

Spatially controlled assembly of phase-separated PSM based on micropatterned palmitic and oleic acid moieties.

As only very minor protein quantities are typically demanded for single molecule applications, production and rapid transfer from mammalian cells is possible (4).

Rapid transfer of transmembrane receptors expressed in HeLa cells into polymer-supported membranes for single molecule fluorescence imaging.

Based on this approach, ligand-induced heterodimerization of the IFN receptor could be quantified in a reconstituted system (4).

Single molecule dimerization of transmembrane IFNAR1 and IFNAR2 in polymer-supported membranes.

Next to transmembrane receptors, reconstitution of integral membrane proteins was achieved including beta-barrel outer membrane proteins, for which spontaneous aggregation into clusters was observed (5).

Micropatterned phase-separated PSMs open exciting perspectives for bioanalytical applications. Based on membrane tethering of His-tagged proteins via tris-NTA lipid, phase partitioning upon dimerization was exploited as a readout for protein-protein interaction (6). Thus, weak binding affinities up to 1 mM could be determined for proteins directly captured to surfaces from mammalian cell lysates (6).

  • Explore the role of lipid composition for transmembrane protein diffusion and interaction.
  • Reconstitute cytosolic domains of receptor signaling complexes.
  • Include spectroscopic probes for quantifying protein conformations at membranes.
Name Institution State
Heinz-Jürgen Steinhoff University of Osnabrück Germany
Ünal Coskun Paul Langerhans Institute Dresden Germany
Jörg Enderlein University of Göttingen Germany
  • Reconstitution of Membrane Proteins into Polymer-supported Membranes for Probing Diffusion and Interactions by Single Molecule Techniques (PDF)
    Analytical Chemistry 83, Nr. 17 (Sep 2011): 6792 - 6799
  • Diffusion and Interaction Dynamics of Individual Membrane Protein Complexes Confined in Micropatterned Polymer-supported Membranes (PDF)
    Small 9, Nr. 4 (Feb 2013): 570 - 577
  • Spatial Organization of Lipid Phases in Micropatterned Polymer-supported Membranes (PDF)
    J. Am. Chem. Soc. 135, Nr. 4 (Jan 2013): 1189 - 1192
  • Supramolecular Assemblies Underpin Turnover of Outer Membrane Proteins in Bacteria (PDF)
    Nature 523, Nr. 7560: 333 - 336 (Jul 2015)
  • Two-Dimensional Trap for Ultrasensitive Quantification of Transient Protein Interactions (PDF)
    ACS Nano, 15 (Sep 2015)

Inorganic nanoparticles provide unique physical properties for visualizing and manipulating cellular processes down to the single molecule level. However, biofunctionalization of these nanoparticles for efficient and stoichiometrically defined conjugation with target proteins without biasing their function remains challenging. We have developed approaches for controlling conjugation stoichiometry by exploiting electrostatic steering of coupling reactions (1, 2). Thus, unbiased diffusion of protein diffusion and interaction at the plasma membrane could be probed using monofunctional quantum dots for cell surface receptor labeling.

Spatiotemporal dynamics of IFN-receptor complexes in living cells visualized by dual color quantum dot tracking.

For efficient nanoparticle targeting inside living cells, we have optimized a substrate for fast, covalent reaction with HaloTag fusion proteins (3). On our quest to apply nanoparticles in the cytosol of living cells, we identified autophagy as a critical mechanism for nanoparticle clearance (4). Using massive PEGylation, monofunctionalized stealth nanoparticles were generated, which were efficiently targeted to a protein in the outer mitochondrial membrane (4).

Magnetogenetic manipulation of Rho GTPase signaling in living cells (5).

Based on these approaches for nanoparticle biofunctionalization, we demonstrated spatially controlled manipulation of active G-protein signaling platforms assembled on the surface of magnetic nanoparticles in living cell (5).

The concept of "magnetogenetic"manipulation opens exciting perspectives as a tool for fundamental cell biology and for medical applications. However, refined surface functionalization and delivery strategies on the basis of sub 50 nm-sized magnetic nanoparticles (6) will be required for practical applications.

  • Nanoparticle functionalization based on protein cages.
  • Generic toolbox for magnetogenetic manipulation.
  • Magnetogenetic manipulation of neuronal cell differentiation.
  • Application of upconversion nanoparticles for cell biology.
Name Institution State
Maxime Dahan Institut Curie, Paris France
Rolf Heumann University of Bochum Germany
Alicia El Haj University of Keele UK
Christine Ménager CNRS UPMC, Paris France
Markus Haase University of Osnabrück Germany
  • FETopen project MAGNEURON
  • Self-controlled monofunctionalization of quantum dots for multiplexed protein tracking in live cells. (PDF)
    Angew. Chem. Int. Ed. Engl., 2010 Jun 1, 49 (24), 4108-12.
  • Electrostatically Controlled Quantum Dot Monofunctionalization for Interrogating the Dynamics of Protein Complexes in Living Cells (PDF)
    ACS Chemical Biology 8, Nr. 2 (Feb 2013): 320 - 326
  • Selective Targeting of Fluorescent Nanoparticles to Proteins Inside Live Cells (PDF)
    Angewandte Chemie International Edition 50, Nr. 40 (Sep 2011): 9352 - 9355
  • Mono-functional Stealth Nanoparticle for Unbiased Single Molecule Tracking Inside Living Cells (PDF)
    Nano Letters 14 (4): 2189 - 95 (Mar 2014)
  • Subcellular Control of Rac-GTPase Signalling by Magnetogenetic Manipulation Inside Living Cells (PDF)
    Nature Nanotechnology 8, Nr. 3 (Mar 2013): 193 - 198
  • Magnetogenetic Control of Protein Gradients inside Living Cells with High Spatial and Temporal Resolution (PDF)
    Nano Letters 15, Nr. 5 : 3487 - 3494 (May 2015)

Protein immobilization on solid support opens versatile possibilities for protein interaction analysis. We have developed surface modification for functional protein immobilization based on site-specific protein capturing. For stable, yet reversible protein immobilization we have developed tris(nitrilotriacetic acid) (tris-NTA), which binds oligohististidine-tagged proteins with nanomolar affinity due to multivalent interactions (1, 2). We have established a large repertoire of molecular tools for surface modification and protein labeling based on tris-NTA (3). For increased specificity and stability of protein capturing, this approach was complemented by enzyme-based coupling techniques including enzymatic phosphopantetheinyl transfer as well as the HaloTag (4). For spatially resolved protein immobilization, we have combined these capturing techniques with soft and photolithographic surface patterning techniques, yielding a versatile toolbox for functional protein organization on surfaces (5, 6).

Microtubule (red) transported by motor proteins (green) immobilized via micropattern tris-NTA (5).

A fundamental objective of these approaches is to develop robust tools for interfacing proteins with surfaces while maintaining the physiological context, e.g. lipid environment of membrane proteins or cellular interaction partners. To this end, we developed micropatterned surface architectures for capturing protein in the plasma membrane of living cells (7, 8).

Surface architecture for capturing HaloTag fusion proteins in the plasma membrane of living cells.

Based on this technique protein-protein interactions at membranes such as receptor hetero-dimerization or effector recruitment can be readily detected and quantified in living cells.

Triggered micropatterning of IFNAR1 (green) in the plasma membrane of living cells followed by ligand-induced association of IFNAR2 (red) (8).

For studying cytosolic protein complexes, we have established surface architectures for pull-down of GFP-tagged proteins from single cells (SiCPull). In combination with single molecule TIRF microscopy, we succeeded to quantify stability and stoichiometry of complexes captured by SiCPull.

Concept of single cell pulldown for quantifying the stability and the stoichiometry of protein complexes (9).

Micropatterned surface capturing of a GFP-tagged cytosolic protein upon cell lysis (9).

By including nanoparticles as additional spectroscopic reporters into micropatterned surface architectures, versatile readouts for biomolecular interactions and conformational changes can be generated. Thus, we implemented label-free detection imaging of protein-protein interactions by localized surface plasmon resonance (LSPR) with micropatterned gold nanoparticles (10).

  • Integrate spectroscopic reporters into surface architecture for quantifying protein conformations in living cells.
  • Detection of protein-lipid interactions by live cell micropatterning.
  • Transfer of membrane proteins for spectroscopic and structural analysis.
Name Institution State
Jürgen Klingauf University of Münster Germany
Thomas Schröder IHP Frankfurt/Oder Germany
Bernd Witzigmann University of Kassel Germany
  • High-affinity adaptors for switchable recognition of histidine-tagged proteins (PDF)
    J. Am. Chem. Soc. 127 (2005) 10205-15.
  • Stable and functional immobilization of histidine-tagged proteins via multivalent chelator head-groups on a molecular poly(ethylene glycol) brush, (PDF)
    Anal. Chem. 77 (2005) 1096 -1105.
  • Multivalent Chelators for Spatially and Temporally Controlled Protein Functionalization (PDF)
    Analytical and Bioanalytical Chemistry 406 (14): 3345 - 57 (May 2014)
  • Functional Immobilization and Patterning of Proteins by an Enzymatic Transfer Reaction (PDF)
    Anal. Chem. 2010, 82, 1478-1485
  • Organization of motor proteins into functional micropatterns fabricated by a photoinduced Fenton reaction., (PDF)
    Angew Chem Int Ed Engl. 48, 9188-91.
  • Maleimide Photolithography for Single-molecule Protein-protein Interaction Analysis in Micropatterns (PDF)
    Analytical Chemistry 83, Nr. 2 (Jan 2011): 501 - 508
  • Live Cell Micropatterning Reveals the Dynamics of Signaling Complexes at the Plasma Membrane (PDF)
    The Journal of Cell Biology 207, Nr. 3 : 407 - 18 (Nov 2014)
  • Spatiotemporally Controlled Reorganization of Signaling Complexes in the Plasma Membrane of Living Cells (PDF)
    Small, (Sep 2015)
  • Single Cell GFP-Trap Reveals Stoichiometry and Dynamics of Cytosolic Protein Complexes (PDF)
    Nano Letters 15, Nr. 5 : 3610 - 3615 (May 2015)
  • Quantitative Real-Time Imaging of Protein-Protein Interactions by LSPR Detection with Micropatterned Gold Nanoparticles (PDF)
    Analytical Chemistry 85, Nr. 20 (Oct 2013): 9564 - 9571

Visualization of cellular processes in living cells with highest spatial and temporal resolution plays a key role in modern cell biology. Recent breakthroughs in overcoming the diffraction limitation in far-field fluorescence microscopy have opened exciting perspectives for live cell imaging. We have focused on single molecule localization microscopy (SMLM) techniques such as fluorescence photoactivation localization microscopy (FPALM) and stochastic optical reconstruction microscopy (STORM). By combining FPALM and direct STORM, we could demonstrate triple color superresolution imaging in living cells (1).

Triple-color superresolution imaging in living cells by combining FPALM (PAGFP and PAmCherry) and dSTORM (ATTO655 coupled via the HaloTag) reveals coorganization of receptor subunits (green, red) in the context of the cortical actin cytoskeleton (blue).

While PALM is typically limited to a single read-out cycle, life cell dSTORM opens exciting possibilities for superresolution imaging of cellular nanostructures over prolonged time scales (1).

Time-lapse superresolution imaging of clathrin dynamics at the plasma membrane using dSTORM (ATTO655).

Time-lapse dual-color TALM imaging of IFNAR2 (green) and its effector protein STAT2 (red).

Classic SMLM requires high overexpression of target proteins in order to achieve sufficient density to fulfill the Nyquist criterion, which may affect cellular functions and morphologies. For SMLM at physiological expression levels, we have introduced tracking and localization microscopy (TALM), which is based on a small ensemble of permanently fluorescent species, which successively explore cellular nanostructures by diffusion in the living cell (2, 3). This technique is particularly applicable to membrane proteins as their mobility is compatible with precise localization. Thus, not only morphologies and proteins mobility, but also connectivities or barriers can be identified. Pair correlation applied to TALM imaging thus provides information about spatial and temporal protein organization, which opens exciting possibilities for identifying and quantifying protein clustering and co-clustering (4).

Application of SMLM on biological questions requires access to dedicated image analysis tools not only for robust localization and tracking of individual emitters, but also for versatile quantification of spatial and temporal properties such as (co-)clustering, co-locomotion, complex stoichiometries or morphologies. We are constantly developing an integrated software package providing versatile tools for such analyses. We share these advanced imaging and evaluation techniques within the framework of the Center of Advanced Light Microscopy of the Biology Department (CALMOS).

  • Establish lattice light sheet microscopy for 3D tracking and localization microscopy.
  • High-density single molecule localization and tracking .
Name Institution State
Eric Betzig Janelia Farm Research Campus US
Stefan Kunis University of Osnabrück Germany
Karin Busch University of Münster Germany
  • Triple-Color Super-Resolution Imaging of Live Cells: Resolving Submicroscopic Receptor Organization in the Plasma Membrane (PDF)
    Angewandte Chemie International Edition 51, Nr. 20 (May 2012): 4868 - 4871
  • Nanoscale organization of mitochondrial microcompartments revealed by combining tracking and localization microscopy (PDF)
    Nano Letters 12, Nr. 2 (Feb 2012): 610 - 616
  • Shuttling of PINK1 between Mitochondrial Microcompartments Resolved by Triple-Color Superresolution Microscopy (PDF)
    ACS Chemical Biology 10, Nr. 9: 1970 - 1976 (Sep 2015)
  • Dynamic Submicroscopic Signaling Zones Revealed by Pair Correlation Tracking and Localization Microscopy (PDF)
    Analytical Chemistry 86, Nr. 17: 8593 - 8602 (Sep 2014)
  • Imaging the Invisible: Resolving Cellular Microcompartments by Superresolution Microscopy Techniques (PDF)
    Biological Chemistry 394, Nr. 9 (Sep 2013): 1097 - 1113
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Functionalization of Nanoparticles.
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Model membranes for GPI-anchored proteins.
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Annett Reichel, Imke Peters, Pia Müller, Ramunas Valiokas, Peter Lamken, Suman Lata, Yvonne Becker, Martynas Gavutis, Eva Jaks, Natalie Al-Furoukh, Irina Ohlmer, Jennifer Julia Strunk, Maniraj Bhagawati, Sharon Waichman, Yulia Podoplelova, Dirk Paterok, Friedrich Roder, David Schmedt, Domenik Liße, Markus Staufenbiel, Oliver Beutel

  • Stephan Wilmes, Oliver Beutel, Zhi Li, Véronique Francois-Newton, Christian P. Richter, Dennis Janning, Cindy Kroll, Patrizia Hanhart, Katharina Hötte, Changjiang You,Gilles Uzé, Sandra Pellegrini, Jacob Piehler
    Receptor Dimerization Dynamics as a Regulatory Valve for Plasticity of Type I Interferon Signaling (PDF)
    The Journal of Cell Biology 209, Nr. 4 : 579 - 593 (May 2015)
    doi:10.1083/jcb.201412049
  • Tim Wedeking, Sara Löchte, Christian P. Richter, Maniraj Bhagawati, Jacob Piehler, Changjiang You
    Single Cell GFP-Trap Reveals Stoichiometry and Dynamics of Cytosolic Protein Complexes (PDF)
    Nano Letters 15, Nr. 5 : 3610 - 3615 (May 2015)
    doi:10.1021/acs.nanolett.5b01153
  • Ignacio Moraga, Gerlinde Wernig, Stephan Wilmes, Vitalina Gryshkova,Christian P. Richter, Wan-Jen Hong, Rahul Sinha, Feng Guo, Hyna Fabionar, Tom S. Wehrman, Peter Krutzik, Samuel Demharter, Isabelle Plo, Irving L. Weissman,Peter Minary, Ravindra Majeti, Stefan N. Constantinescu, Jacob Piehler, K. Christopher Garcia
    Tuning Cytokine Receptor Signaling by Re-Orienting Dimer Geometry with Surrogate Ligands (PDF)
    Cell 160, Nr. 6 : 1169 - 1208 (Mar 2015)
    doi:10.1016/j.cell.2015.02.011
  • Sara Löchte, Sharon Waichman, Oliver Beutel, Changjiang You, Jacob Piehler
    Live Cell Micropatterning Reveals the Dynamics of Signaling Complexes at the Plasma Membrane (PDF)
    The Journal of Cell Biology 207, Nr. 3 : 407 - 18 (Nov 2014)
    doi:10.1083/jcb.201406032
  • Oliver Beutel, Jörg Nikolaus, Oliver Birkholz, Changjiang You, Thomas Schmidt,Andreas Herrmann, Jacob Piehler
    High-Fidelity Protein Targeting into Membrane Lipid Microdomains in Living Cells (PDF)
    Angewandte Chemie International Edition 53, Nr. 5 (Jan 2014): 1311 - 1315
    doi:10.1002/anie.201306328
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    Rapid Transfer of Transmembrane Proteins for Single Molecule Dimerization Assays in Polymer-Supported Membranes (PDF)
    ACS Chemical Biology 9, Nr. 11 : 2479 - 84 (Nov 2014)
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    High Efficiency Cell-Specific Targeting of Cytokine Activity (PDF)
    Nature Communications 5 (Jan 2014): 3016
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    Spatial Organization of Lipid Phases in Micropatterned Polymer-supported Membranes (PDF)
    J. Am. Chem. Soc. 135, Nr. 4 (Jan 2013): 1189 - 1192
    doi:10.1021/ja310186g
  • Stephan Wilmes, Markus Staufenbiel, Domenik Liße, Christian P. Richter, Oliver Beutel, Karin B. Busch, Samuel T. Hess, Jacob Piehler
    Triple-Color Super-Resolution Imaging of Live Cells: Resolving Submicroscopic Receptor Organization in the Plasma Membrane (PDF)
    Angewandte Chemie International Edition 51, Nr. 20 (May 2012): 4868 - 4871
    doi:10.1002/anie.201200853
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    Structural Linkage Between Ligand Discrimination and Receptor Activation by Type I Interferons (PDF)
    Cell 146, Nr. 4 (Aug 2011): 621 - 632
    doi:10.1016/j.cell.2011.06.048
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    Monitoring Changes in the Oligomeric State of a Candidate Endoplasmic Reticulum (ER) Ceramide Sensor by Single-Molecule Photobleaching
    The Journal of Biological Chemistry 291, Nr. 47: 24735-46 (Nov 2016)
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    Rapid Dynamics of General Transcription Factor TFIIB Binding during Preinitiation Complex Assembly Revealed by Single-Molecule Analysis (PDF)
    Genes & Development 30, Nr. 18: 2106-18 (Sep 2016)
    doi:10.1101/gad.285395.116
  • Christoph Drees, Athira Naduviledathu Raj, Rainer Kurre, Karin B. Busch, Markus Haase, Jacob Piehler
    Engineered Upconversion Nanoparticles for Resolving Protein Interactions inside Living Cells (PDF)
    Angewandte Chemie International Edition (Aug 2016)
    doi:10.1002/anie.201603028
  • Britta Barlag, Oliver Beutel, Dennis Janning, Frederik Czarniak, Christian P. Richter, Carina Kommnick, Vera Göser, Rainer Kurre, Florian Fabiani, Marc Erhardt, Jacob Piehler, Michael Hensel
    Single Molecule Super-Resolution Imaging of Proteins in Living Salmonella Enterica Using Self-Labelling Enzymes (PDF)
    Scientific Reports 6: 31601 (Aug 2016)
    doi:10.1038/srep31601
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    Nucleic Acids Research 44, Nr. 13: 6363-76 (Jul 2016)
    doi:10.1093/nar/gkw518
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    Interferon Alpha Subtype-Specific Suppression of HIV-1 Infection In Vivo (PDF)
    Journal of Virology 90, Nr. 13: 6001–13 (Jul 2016)
    doi:10.1128/JVI.00451-16
  • Scott D. Speer, Zhi Li, Sofija Buta, Béatrice Payelle-Brogard, Li Qian, Frederic Vigant, Erminia Rubino, Thomas J. Gardner, Tim Wedeking, Mark Hermann, James Duehr, Ozden Sanal, Ilhan Tezcan, Nahal Mansouri, Payam Tabarsi, Davood Mansouri, Véronique Francois-Newton, Coralie F. Daussy, Marisela R. Rodriguez, Deborah J. Lenschow, Alexander N. Freiberg, Domenico Tortorella, Jacob Piehler, Benhur Lee, Adolfo García-Sastre, Sandra Pellegrini, Dusan Bogunovic
    ISG15 Deficiency and Increased Viral Resistance in Humans but Not Mice (PDF)
    Nature Communications 7 (May 2016)
    doi:10.1038/ncomms11496
  • Raphael Zahn, Dino Osmanović, Severin Ehret, Carolina Araya Callis, Steffen Frey, Murray Stewart, Changjiang You, Dirk Görlich, Bart W. Hoogenboom, Ralf P. Richter
    A Physical Model Describing the Interaction of Nuclear Transport Receptors with FG Nucleoporin Domain Assemblies (PDF)
    eLife 5 (Apr 2016)
    doi:10.7554/eLife.14119
  • Changjiang You, Jacob Piehler
    Functional protein micropatterning for drug design and discovery (PDF)
    Expert Opinion on Drug Discovery 11, Nr. 1: 105–19 (2016)
    doi:10.1517/17460441.2016.1109625
  • Anna Eichler-Volf, Alexander Kovalev, Tim Wedeking, Elena V. Gorb, Longjian Xue, Changjiang You, Jacob Piehler, Stanislav N. Gorb, Martin Steinhart
    Bioinspired Monolithic Polymer Microsphere Arrays as Generically Anti-Adhesive Surfaces (PDF)
    Bioinspiration & Biomimetics 11, Nr. 2: 25002 (Mar 2016)
    doi:10.1088/1748-3190/11/2/025002
  • Ignacio Moraga, David Richter, Stephan Wilmes, Hauke Winkelmann, Kevin Jude, Christoph Thomas,Megan M. Suhoski, Edgar G. Engleman, Jacob Piehler, K. Christopher Garcia
    Instructive Roles for Cytokine-Receptor Binding Parameters in Determining Signaling and Functional Potency (PDF)
    Science Signaling 8, Nr. 402 (Sep 2015)
    doi:10.1126/scisignal.aab2677
  • Tim Wedeking , Sara Löchte, Oliver Birkholz, Alexander Wallenstein, Julia Trahe, Jürgen Klingauf, Jacob Piehler, Changjiang You
    Spatiotemporally Controlled Reorganization of Signaling Complexes in the Plasma Membrane of Living Cells (PDF)
    Small, (Sep 2015)
    doi:10.1002/smll.201502132
  • Oliver Beutel, Friedrich Roder, Oliver Birkholz, Christian Rickert, Heinz-Jürgen Steinhoff, Michal Grzybek, Ünal Coskun, Jacob Piehler
    Two-Dimensional Trap for Ultrasensitive Quantification of Transient Protein Interactions (PDF)
    ACS Nano, 15 (Sep 2015)
    doi:10.1021/acsnano.5b02696
  • Felix R. M. Beinlich, Christoph Drees, Jacob Piehler, Karin B. Busch
    Shuttling of PINK1 between Mitochondrial Microcompartments Resolved by Triple-Color Superresolution Microscopy (PDF)
    ACS Chemical Biology 10, Nr. 9: 1970 - 1976 (Sep 2015)
    doi:10.1021/acschembio.5b00295
  • Matthew J. Peel, Stephen J. Cross, Oliver Birkholz, Amine Aladag, Jacob Piehler, Suman Peel
    Rupture of Stochastically Occurring Vesicle Clusters Limits Bilayer Formation on Alkane-PEG-Type Supports: Uncoupling Clustering from Surface Coverage (PDF)
    Langmuir: The ACS Journal of Surfaces and Colloids 31, Nr. 32: 8830 - 8840 (Aug 2015)
    doi:10.1021/acs.langmuir.5b00925
  • Patrice Rassam, Nikki A. Copeland, Oliver Birkholz, Csaba Tóth, Matthieu Chavent, Anna L. Duncan,Stephen J. Cross, Nicholas G. Housden, Renata Kaminska, Urban Seger, Diana M. Quinn, Tamsin J. Garrod, Mark S. P. Sansom, Jacob Piehler, Christoph G. Baumann, Colin Kleanthous
    Supramolecular Assemblies Underpin Turnover of Outer Membrane Proteins in Bacteria (PDF)
    Nature 523, Nr. 7560: 333 - 336 (Jul 2015)
    doi:10.1038/nature14461
  • Davide Normanno, Lydia Boudarène, Claire Dugast-Darzacq, Jiji Chen, Christian Richter, Florence Proux, Olivier Bénichou, Raphaël Voituriez, Xavier Darzacq, Maxime Dahan
    Probing the Target Search of DNA-Binding Proteins in Mammalian Cells Using TetR as Model Searcher (PDF)
    Nature Communications 6 (Jul 2015)
    doi:10.1038/ncomms8357
  • Stephan Wilmes, Oliver Beutel, Zhi Li, Véronique Francois-Newton, Christian P. Richter, Dennis Janning, Cindy Kroll, Patrizia Hanhart, Katharina Hötte, Changjiang You,Gilles Uzé, Sandra Pellegrini, Jacob Piehler
    Receptor Dimerization Dynamics as a Regulatory Valve for Plasticity of Type I Interferon Signaling (PDF)
    The Journal of Cell Biology 209, Nr. 4 : 579 - 593 (May 2015)
    doi:10.1083/jcb.201412049
  • Tim Wedeking, Sara Löchte, Christian P. Richter, Maniraj Bhagawati, Jacob Piehler, Changjiang You
    Single Cell GFP-Trap Reveals Stoichiometry and Dynamics of Cytosolic Protein Complexes (PDF)
    Nano Letters 15, Nr. 5 : 3610 - 3615 (May 2015)
    doi:10.1021/acs.nanolett.5b01153
  • Fred Etoc, Chiara Vicario, Domenik Liße, Jean-Michel Siaugue, Jacob Piehler, Mathieu Coppey, Maxime Dahan
    Magnetogenetic Control of Protein Gradients inside Living Cells with High Spatial and Temporal Resolution (PDF)
    Nano Letters 15, Nr. 5 : 3487 - 3494 (May 2015)
    doi:10.1021/acs.nanolett.5b00851
  • Ignacio Moraga, Gerlinde Wernig, Stephan Wilmes, Vitalina Gryshkova,Christian P. Richter, Wan-Jen Hong, Rahul Sinha, Feng Guo, Hyna Fabionar, Tom S. Wehrman, Peter Krutzik, Samuel Demharter, Isabelle Plo, Irving L. Weissman,Peter Minary, Ravindra Majeti, Stefan N. Constantinescu, Jacob Piehler, K. Christopher Garcia
    Tuning Cytokine Receptor Signaling by Re-Orienting Dimer Geometry with Surrogate Ligands (PDF)
    Cell 160, Nr. 6 : 1169 - 1208 (Mar 2015)
    doi:10.1016/j.cell.2015.02.011
  • Henning Arlt, Kathrin Auffarth, Rainer Kurre, Domenik Liße, Jacob Piehler, Christian Ungermann
    Spatiotemporal Dynamics of Membrane Remodeling and Fusion Proteins during Endocytic Transport (PDF)
    Molecular Biology of the Cell 26, Nr. 7 : 1357 - 1370 (Apr 2015)
    doi:10.1091/mbc.E14-08-1318
  • Gideon Schreiber, Jacob Piehler
    The Molecular Basis for Functional Plasticity in Type I Interferon Signaling (PDF)
    Trends in Immunology 36, Nr. 3 : 139 - 149 (Mar 2015)
    doi:10.1016/j.it.2015.01.002
  • Ioan Orban-Glaß, Natalia Voskoboynikova, Karin B. Busch, Daniel Klose,Christian Rickert, Wageiha Mosslehy, Friedrich Roder, Verena, Wilkens, Jacob Piehler, Martin Engelhard, Heinz-Jürgen Steinhoff, Johann P. Klare
    Clustering and Dynamics of Phototransducer Signaling Domains Revealed by Site-Directed Spin Labeling Electron Paramagnetic Resonance on SRII/HtrIIin Membranes and Nanodiscs (PDF)
    Biochemistry 54, Nr. 2 : 349 - 62 (Jan 2015)
    doi:10.1021/bi501160q
  • Sara Löchte, Sharon Waichman, Oliver Beutel, Changjiang You, Jacob Piehler
    Live Cell Micropatterning Reveals the Dynamics of Signaling Complexes at the Plasma Membrane (PDF)
    The Journal of Cell Biology 207, Nr. 3 : 407 - 18 (Nov 2014)
    doi:10.1083/jcb.201406032
  • Friedrich Roder, Stephan Wilmes, Christian P. Richter, Jacob Piehler
    Rapid Transfer of Transmembrane Proteins for Single Molecule Dimerization Assays in Polymer-Supported Membranes (PDF)
    ACS Chemical Biology 9, Nr. 11 : 2479 - 84 (Nov 2014)
    doi:10.1021/cb5005806
  • Changjiang You, Christian P. Richter, Sara Löchte, Stephan Wilmes, Jacob Piehler
    Dynamic Submicroscopic Signaling Zones Revealed by Pair Correlation Tracking and Localization Microscopy (PDF)
    Analytical Chemistry 86, Nr. 17: 8593 - 8602 (Sep 2014)
    doi:10.1021/ac501127r
  • Dennis Janning, Maxim Igaev, Frederik Sündermann, Jörg Brühmann, Oliver Beutel, Jürgen J. Heinisch, Lidia Bakota, Jacob Piehler, Wolfgang Junge, Roland Brandt
    Single Molecule Tracking of Tau Reveals Fast Kiss-and-Hop Interaction with Microtubules in Living Neurons (PDF)
    Molecular Biology of the Cell, 27 (Aug 2014)
    doi:10.1091/mbc.E14-06-1099
  • Changjiang You, Jacob Piehler
    Multivalent Chelators for Spatially and Temporally Controlled Protein Functionalization (PDF)
    Analytical and Bioanalytical Chemistry 406 (14): 3345 - 57 (May 2014)
    doi:10.1007/s00216-014-7803-y
  • Domenik Liße, Christian P. Richter, Christoph Drees, Oliver Birkholz, Changjiang You,Enrico Rampazzo, Jacob Piehler
    Mono-functional Stealth Nanoparticle for Unbiased Single Molecule Tracking Inside Living Cells (PDF)
    Nano Letters 14 (4): 2189 - 95 (Mar 2014)
    doi:10.1021/nl500637a
  • Jacob Piehler
    Spectroscopic techniques for monitoring protein interactions in living cells (PDF)
    Current Opinion in Structural Biology 24 (Feb 2014): 54 - 62
    doi:10.1038/ncomms4016
  • Oliver Beutel, Jörg Nikolaus, Oliver Birkholz, Changjiang You, Thomas Schmidt,Andreas Herrmann, Jacob Piehler
    High-Fidelity Protein Targeting into Membrane Lipid Microdomains in Living Cells (PDF)
    Angewandte Chemie International Edition 53, Nr. 5 (Jan 2014): 1311 - 1315
    doi:10.1002/anie.201306328
  • Núria Taberner, Georges Weber, Changjiang You, Roland Dries, Jacob Piehler, Marileen Dogterom
    Reconstituting Functional Microtubule-Barrier Interactions (PDF)
    Methods in Cell Biology 120 (2014): 69 - 90
    doi:10.1016/B978-0-12-417136-7.00005-7
  • Margarita Cabrera, Mirjana Nordmann, Angela Perz, David Schmedt, Andreas Gerondopoulos,Francis Barr, Jacob Piehler, Siegfried Engelbrecht-Vandré, Christian Ungermann
    The Mon1-Ccz1 GEF Activates the Rab7 GTPase Ypt7 via a Longin Fold-Rab Interface andAssociation with PI-3-P-Positive Membranes (PDF)
    Journal of Cell Science (Jan 2014)
    doi:10.1242/jcs.140921
  • Geneviève Garcin, Franciane Paul, Markus Staufenbiel, Yann Bordat, José Van der Heyden,Stephan Wilmes, Guillaume Cartron, Florence Apparailly, Stefaan De Koker, Jacob Piehler,Jan Tavernier, Gilles Uzé
    High Efficiency Cell-Specific Targeting of Cytokine Activity (PDF)
    Nature Communications 5 (Jan 2014): 3016
    doi:10.1038/ncomms4016
  • Jiangguo Lin, Preston Countryman, Noah Buncher, Parminder Kaur, Longjiang E, Yiyun Zhang, Greg Gibson, Changjiang You, Simon C. Watkins, Jacob Piehler, Patricia L. Opresko, Neil M. Kad, Hong Wang
    TRF1 and TRF2 Use Different Mechanisms to Find Telomeric DNA but Share a Novel Mechanism to Search for Protein Partners at Telomeres (PDF)
    Nucleic Acids Research (Nov 2013): 1 - 12
    doi:10.1093/nar/gkt1132
  • Maniraj Bhagawati, Changjiang You, Jacob Piehler
    Quantitative Real-Time Imaging of Protein-Protein Interactions by LSPR Detection with Micropatterned Gold Nanoparticles (PDF)
    Analytical Chemistry 85, Nr. 20 (Oct 2013): 9564 - 9571
    doi:10.1021/ac401673e
  • Michael Hensel, Jürgen Klingauf, Jacob Piehler
    Imaging the Invisible: Resolving Cellular Microcompartments by Superresolution Microscopy Techniques (PDF)
    Biological Chemistry 394, Nr. 9 (Sep 2013): 1097 - 1113
    doi:10.1515/hsz-2012-0324
  • Pia J. Müller, Kristoffer T. G. Rigbolt, Dirk Paterok, Jacob Piehler, Jens Vanselow, Edwin Lasonder, Jens S. Andersen, Fred Schaper, Radoslaw M. Sobota
    Protein Tyrosine Phosphatase SHP2/PTPN11 Mistargeting as a Consequence of SH2-domain Point Mutations Associated with Noonan Syndrome and Leukemia (PDF)
    Journal of Proteomics 84 (Jun 2013): 132 - 147
    doi:10.1016/j.jprot.2013.04.005
  • Jen-Wei Chang, Yi-Min Wu, Zi-Yun Chen, Shih-Hsin Huang, Chun-Hsiung Wang, Pei-Lun Wu, Yi-Ping Weng, Changjiang You, Jacob Piehler, Wei-Hau Chang
    Hybrid Electron microscopy-FRET Imaging Localizes the Dynamical C-terminus of Tfg2 in RNA Polymerase II-TFIIF with Nanometer Precision (PDF)
    Journal of Structural Biology 184 (Jun 2013): 52 - 62
    doi:10.1016/j.jsb.2013.05.015
  • Mihaela Gropeanu, Maniraj Bhagawati, Radu A. Gropeanu, Gemma M. Rodríguez Muñiz, Subramanian Sundaram, Jacob Piehler, Aránzazu del Campo
    A Versatile Toolbox for Multiplexed Protein Micropatterning by Laser Lithography (PDF)
    Small 9, Nr. 6 (Mar 2013): 838 - 845
    doi:10.1002/smll.201201901
  • Fred Etoc, Domenik Liße, Yohanns Bellaïche, Jacob Piehler, Mathieu Coppey, Maxime Dahan
    Subcellular Control of Rac-GTPase Signalling by Magnetogenetic Manipulation Inside Living Cells (PDF)
    Nature Nanotechnology 8, Nr. 3 (Mar 2013): 193 - 198
    doi:10.1038/nnano.2013.23
  • Sharon Waichman, Friedrich Roder, Christian P. Richter, Oliver Birkholz, Jacob Piehler
    Diffusion and Interaction Dynamics of Individual Membrane Protein Complexes Confined in Micropatterned Polymer-supported Membranes (PDF)
    Small 9, Nr. 4 (Feb 2013): 570 - 577
    doi:10.1002/smll.201201530
  • Changjiang You, Stephan Wilmes, Christian P. Richter, Oliver Beutel, Domenik Liße, Jacob Piehler
    Electrostatically Controlled Quantum Dot Monofunctionalization for Interrogating the Dynamics of Protein Complexes in Living Cells (PDF)
    ACS Chemical Biology 8, Nr. 2 (Feb 2013): 320 - 326
    doi:10.1021/cb300543t
  • Friedrich Roder, Oliver Birkholz, Oliver Beutel, Dirk Paterok, Jacob Piehler
    Spatial Organization of Lipid Phases in Micropatterned Polymer-supported Membranes (PDF)
    J. Am. Chem. Soc. 135, Nr. 4 (Jan 2013): 1189 - 1192
    doi:10.1021/ja310186g
  • Geneviève Garcin, Yann Bordat, Paul Chuchana, Danièle Monneron, Helen K. W. Law, Jacob Piehler, Gilles Uzé
    Differential Activity of Type I Interferon Subtypes for Dendritic Cell Differentiation (PDF)
    PloS One 8, Nr. 3 (2013)
    doi:10.1371/journal.pone.0058465
  • Jacob Piehler, Christoph Thomas, K. Christopher Garcia, Gideon Schreiber
    Structural and Dynamic Determinants of Type I Interferon Receptor Assembly and Their Functional Interpretation (PDF)
    Immunological Reviews 250, Nr. 1 (Nov 2012): 317 - 334
    doi:10.1111/imr.12001
  • Stephan Wilmes, Markus Staufenbiel, Domenik Liße, Christian P. Richter, Oliver Beutel, Karin B. Busch, Samuel T. Hess, Jacob Piehler
    Triple-Color Super-Resolution Imaging of Live Cells: Resolving Submicroscopic Receptor Organization in the Plasma Membrane (PDF)
    Angewandte Chemie International Edition 51, Nr. 20 (May 2012): 4868 - 4871
    doi:10.1002/anie.201200853
  • Timo Appelhans, Christian P. Richter, Verena Wilkens, Samuel T. Hess, Jacob Piehler, Karin B. Busch
    Nanoscale organization of mitochondrial microcompartments revealed by combining tracking and localization microscopy (PDF)
    Nano Letters 12, Nr. 2 (Feb 2012): 610 - 616
    doi:10.1021/nl203343a
  • Domenik Liße, Verena Wilkens, Changjiang You, Karin B. Busch, Jacob Piehler
    Selective Targeting of Fluorescent Nanoparticles to Proteins Inside Live Cells (PDF)
    Angewandte Chemie International Edition 50, Nr. 40 (Sep 2011): 9352 - 9355
    doi:10.1002/anie.201101499
  • Friedrich Roder, Sharon Waichman, Dirk Paterok, Robin Schubert, Christian P. Richter, Bo Liedberg, Jacob Piehler
    Reconstitution of Membrane Proteins into Polymer-supported Membranes for Probing Diffusion and Interactions by Single Molecule Techniques (PDF)
    Analytical Chemistry 83, Nr. 17 (Sep 2011): 6792 - 6799
    doi:10.1021/ac201294v
  • Christoph Thomas, Ignacio Moraga, Doron Levin, Peter O. Krutzik, Yulia Podoplelova, Angelica Trejo, Choongho Lee, Ganit Yarden, Susan E. Vleck, Jeffrey S. Glenn, Garry P. Nolan, Jacob Piehler, Gideon Schreiber, K. Christopher Garcia
    Structural Linkage Between Ligand Discrimination and Receptor Activation by Type I Interferons (PDF)
    Cell 146, Nr. 4 (Aug 2011): 621 - 632
    doi:10.1016/j.cell.2011.06.048
  • Jacob Piehler
    GPCRs: Caught in a Spectroscopic Trap (PDF)
    Nature Chemical Biology 7, Nr. 9 (Sep 2011): 578 - 579
    doi:10.1038/nchembio.641
  • Véronique François-Newton, Gabriel Magno de Freitas Almeida, Béatrice Payelle-Brogard, Danièle Monneron, Lydiane Pichard-Garcia, Jacob Piehler, Sandra Pellegrini, Gilles Uzé
    USP18-based Negative Feedback Control Is Induced by Type I and Type III Interferons and Specifically Inactivates Interferon alpha Response (PDF)
    PloS One 6, Nr. 7 (Jul 2011): e22200
    doi:10.1371/journal.pone.0022200
  • Marta Alvarez, José Maria Alonso, Oscar Filevich, Maniraj Bhagawati, Roberto Etchenique, Jacob Piehler, Aranzazu Del Campo
    Modulating Surface Density of Proteins via Caged Surfaces and Controlled Light Exposure (PDF)
    Langmuir 27, Nr. 6 (Feb 2011): 2789 - 2795
    doi:10.1021/la104511x
  • Sharon Waichman, Changjiang You, Oliver Beutel, Maniraj Bhagawati, und Jacob Piehler
    Maleimide Photolithography for Single-molecule Protein-protein Interaction Analysis in Micropatterns (PDF)
    Analytical Chemistry 83, Nr. 2 (Jan 2011): 501 - 508
    doi:10.1021/ac1021453
  • DeRocco V., Anderson T., Piehler J., Erie D.A., Weninger K.
    Four-color single-molecule fluorescence with noncovalent dye labeling to monitor dynamic multimolecular complexes. (PDF)
    Biotechniques. 2010 Nov;49(5):807-16.
  • Clarke, S., Pinaud, F., Beutel, O., You, C., Piehler, J., Dahan, M.
    Covalent monofunctionalization of peptide-coated quantum dots for single-molecule assays. (PDF)
    Nano Lett., 2010 Jun 9, 10 (6), 2147-54.
  • You, C., Wilmes, S., Beutel, O., Löchte, S., Podoplelowa, Y., Roder, F., Richter, C., Seine, T., Schaible, D., Uzé, G., Clarke, S., Pinaud, F., Dahan, M., Piehler, J.
    Self-controlled monofunctionalization of quantum dots for multiplexed protein tracking in live cells. (PDF)
    Angew. Chem. Int. Ed. Engl., 2010 Jun 1, 49 (24), 4108-12.
  • Bhagawati, M., Lata, S., Tampé, R., Piehler, J.*
    Native Laser Lithography of His-Tagged Proteins by Uncaging of Multivalent Chelators. (PDF)
    J. Am. Chem. Soc., 2010 May 5, 132 (17), 5932-3.
  • Eisele, N.B., Frey, S., Piehler, J., Görlich, D., Richter, R.P.
    Ultrathin nucleoporin phenylalanine-glycine repeat films and their interaction with nuclear transport receptors. (PDF)
    EMBO Rep. 2010 May, 11 (5), 366-72.
  • Grunwald C., Schulze K., Reichel A., Weiss V.U., Blaas D., Piehler J., Wiesmüller K.H., Tampé R.
    In situ assembly of macromolecular complexes triggered by light. (PDF)
    Proc. Natl. Acad. Sci. USA. 2010 Apr 6, 107 (14), 6146-51.
  • Akabayov, S.R., Biron, Z., Lamken, P., Piehler, J. and Anglister, J.]
    NMR Mapping of the IFNAR1-EC Binding Site on IFN alpha2 Reveals Allosteric Changes in the IFNAR2-EC Binding Site (PDF)
    Biochemistry, 2010, 49 (4), 687-695
  • Waichman, S., Bhagawati, M., Podoplelova, Y., Reichel A., Brunk, A., Paterok, D., and Piehler, J.]
    Functional Immobilization and Patterning of Proteins by an Enzymatic Transfer Reaction (PDF)
    Anal. Chem. 2010, 82, 1478-1485
  • André T., Reichel A., Wiesmüller K.H., Tampé R., Piehler J., Brock R.,
    Selectivity of competitive multivalent interactions at interfaces., (PDF)
    Chembiochem. 10, 1878-87.
  • Wruss J., Pollheimer P.D., Meindl I., Reichel A., Schulze K., Schöfberger W., Piehler J., Tampé R., Blaas D., Gruber H.J.,
    Conformation of Receptor Adopted upon Interaction with Virus Revealed by Site-Specific Fluorescence Quenchers and FRET Analysis., (PDF)
    J. Am. Chem. Soc., 2009, 131 (15), 5478 - 82
  • Bhagawati M., Ghosh S., Reichel A., Froehner K., Surrey T., Piehler J.,
    Organization of motor proteins into functional micropatterns fabricated by a photoinduced Fenton reaction., (PDF)
    Angew Chem Int Ed Engl. 48, 9188-91.
  • Koide A., Wojcik J., Gilbreth R.N., Reichel A., Piehler J., Koide S.,
    Accelerating phage-display library selection by reversible and site-specific biotinylation., (PDF)
    Protein Eng Des Sel 22, 685-90.
  • You, C., Bhagawati, M., Brecht, A. & Piehler, J.,
    Affinity capturing for targeting proteins into micro and nanostructures., (PDF)
    Anal Bioanal Chem 393, 1563-70.
  • Strunk, J. J., Gregor, I., Becker, Y., Lamken, P., Lata, S., Reichel, A., Enderlein, J. & Piehler, J.,
    Probing protein conformations by in situ non-covalent fluorescence labeling., (PDF)
    Bioconjug Chem 20, 41-6.
  • Roullier, V., Clarke, S., You, C., Pinaud, F., Gouzer, G. G., Schaible, D., Marchi-Artzner, V., Piehler, J. & Dahan, M.,
    High-affinity labeling and tracking of individual histidine-tagged proteins in live cells using Ni2+ ntris-nitrilotriacetic acid quantum dot conjugates., (PDF)
    Nano Lett 9, 1228-34.
  • Rakickas, T., Gavutis, M., Reichel, A., Piehler, J., Liedberg, B. & Valiokas, R.,
    Protein-Protein Interactions in Reversibly Assembled Nanopatterns., (PDF)
    Nano Lett 8, 3369-75.
  • Lata, S., Schoehn, G., Jain, A., Pires, R., Piehler, J., Gottlinger, H. G. & Weissenhorn, W.,
    Helical Structures of ESCRT-III Are Disassembled by VPS4., (PDF)
    Science 321, 1354-7.
  • Klenkar, G., Briana, B., Ederth, T., Stengel, G., Höök, F., Piehler, J. & Liedberg, B.,
    Addressable adsorption of lipid vesicles and subsequent protein interaction studies., (PDF)
    Biointerphases 3, 29-37.
  • Kalie, E., Jaitin, D. A., Podoplelova, Y., Piehler, J. & Schreiber, G.,
    The stability of the ternary interferon-receptor complex rather than the affinity to the individual subunits dictates differential biological activities., (PDF)
    J Biol Chem 283, 32925-36.
  • Bieling, P., Telley, I. A., Piehler, J. & Surrey, T.,
    Processive kinesins require loose mechanical coupling for efficient collective motility., (PDF)
    EMBO Rep 9, 1121-7.
  • Rashid, U. J., Hoffmann, J., Brutschy, B., Piehler, J. & Chen, J. C.,
    Multiple targets for suppression of RNA interference by tomato aspermy virus protein 2B., (PDF)
    Biochemistry 47, 12655-7.
  • Valiokas R., Klenkar G., Tinazli A., Reichel A., Tampe R., Piehler J., Liedberg B.,
    Self-Assembled Monolayers With Terminal Mono-, Bis- and Tris-nitrilotriacetic Acid Groups: Characterization and Application., (PDF)
    Langmuir (2008) 24, 4959-4967.
  • Strunk J. J., Gregor I., Becker Y., Li Z., Gavutis M., Jaks E., Lamken P., Walz T., Enderlein J., Piehler J.,
    Ligand binding induces a conformational change in ifnar1 that is propagated to its membrane-proximal domain, (PDF)
    J. Mol. Biol. 377 (2008) 725-739.
  • Li Z., Strunk J. J., Lamken P., Piehler J., Walz T.,
    The EM structure of a type I interferon - receptor complex reveals a novel mechanism for cytokine signaling, (PDF)
    J. Mol. Biol. 377 (2008) 715-724.
  • Alonso J., Reichel A., Piehler J, Del Campo A.,
    Photopatterned surfaces for site-specific and functional immobilization of proteins, (PDF)
    Langmuir 24 (2008) 448-457.
  • Thelen K., Wolfram, T., Maier B., Jährling S., Tinazli A., Piehler J., Spatz J.P., Pollerberg G.E.,
    Cell adhesion molecule DM-GRASP presented as nanopatterns to neurons regulates attachment and neurite growth, (PDF)
    Soft Matter 3 (2007) 1486 - 1491.
  • Uzé; G., Schreiber G., Piehler J., Pellegrini S.,
    The receptor of the type I interferon family, (PDF)
    Curr Top Microbiol Immunol. 316 (2007) 71-95.
  • Reichel A., Schaible D., Al Furoukh N., Cohen M., Schreiber G., Piehler J,
    Non-covalent, site-specific biotinylation of histidine-tagged proteins, (PDF)
    Anal. Chem. 79 (2007) 8590-8600.
  • Rashid U.J., Paterok D., Koglin A., Gohlke H., Piehler J., Chen J.C.,
    Structure of Aquifex aeolicus argonaute highlights conformational flexibility of the PAZ domain as a potential regulator of RNA-induced silencing complex function, (PDF)
    J. Biol. Chem. 282 (2007) 13824-13832.
  • Klammt C., Schwarz D., Eifler N., Engel A., Piehler J., Haase W., Hahn S., Dötsch V., Bernhard F.,
    Cell-free production of G protein-coupled receptors for functional and structural studies, (PDF)
    J. Struct. Biol. 158 (2007) 482 - 493.
  • Tinazli A., Piehler J., Beuttler M., Guckenberger R., Tampé R.,
    Native protein nanolithography that can write, read and erase, (PDF)
    Nature Nanotechnology 2 (2007) 220-225.
  • Jaks E., Gavutis M., Uzé, G., Martal J., Piehler J.,
    Differential receptor subunit affinities of type I interferons govern differential signal activation, (PDF)
    J. Mol. Biol. 366 (2007) 525-539.
  • Gavutis M., Lata S., Piehler J.,
    Probing 2-dimensional protein-protein interactions on model membranes, (PDF)
    Nature Protocols 1 (2006) 2091-2103.
  • Lata S., Piehler J.,
    Synthesis of a multivalent chelator lipid for stably tethering histidine-tagged proteins onto membranes, (PDF)
    Nature Protocols 1 (2006) 2104-2109.
  • Valiokas R., Klenkar G., Tinazli A., Tampé; R., Liedberg B., Piehler J.,
    Differential protein assembly on micropatterned surfaces with tailored molecular and surface multivalency, (PDF)
    ChemBioChem 7 (2006) 1325-1329.
  • Klenkar G., Valiokas R., Lundstrom I., Tinazli A., Tampé; R., Piehler J., Liedberg B.,
    Piezo-dispensed microarray of multivalent chelating thiols for dissecting complex protein-protein interactions, (PDF)
    Anal. Chem. 78 (2006) 3643-3650.
  • Lata, S., Gavutis, M., Tampé;, R., Piehler, J.,
    Specific and stable fluorescence labeling of histidine-tagged proteins for studying multi-protein interactions, (PDF)
    J. Am. Chem. Soc. 128 (2006) 2365-2372.
  • Renner, C., Piehler, J., Schrader, T.,
    Arginine- and Lysine-Specific Polymers for Protein Recognition and Immobilization, (PDF)
    J. Am. Chem. Soc. 128 (2006) 620-628.
  • Gavutis, M., Jaks, E. Lamken, P.,Piehler, J.,
    Determination of the 2-dimensional interaction rate constants of a cytokine receptor complex, (PDF)
    Biophys. J. 90 (2006) 3345-3355.
  • Lata, S., Gavutis, M., Piehler, J.,
    Monitoring the dynamics of ligand-receptor complexes on model membranes, (PDF)
    J. Am. Chem. Soc. 128 (2006) 6-7.
  • Jaitin D., Roisman L.C., Jaks E., Gavutis M., Piehler J., Van der Heyden J., Uze G., Schreiber G.,
    Inquiring into the differential actions of interferons: an IFNalpha2 mutant endowed with enhanced binding affinity to IFNAR1 is functionally similar to IFNbeta, (PDF)
    Mol. Cell. Biol. 26 (2006) 1888-1897.
  • Lata, S., Reichel, A., Brock R., Tampé, R., Piehler, J.,
    High-affinity adaptors for switchable recognition of histidine-tagged proteins, (PDF)
    J. Am. Chem. Soc. 127 (2005) 10205-15.
  • Lamken, P., Gavutis, M., Peters, I., Van der Heyden, J., Uze, G., Piehler, J.,
    Functional cartography of the extracellular domain of the type I interferon receptor subunit ifnar1, (PDF)
    J. Mol. Biol. 350 (2005) 476 - 488.
  • Tinazli, A., Tang, J., Valiokas, R., Picuric, S., Lata, S., Piehler, J., Liedberg, B., Tampé, R.,
    Multivalent, self-organizing chelator thiols for stable and switchable immobilization of histidine-tagged proteins at micro arrays, (PDF)
    Chem. Eur. J. 11 (2005) 5249 - 5259.
  • Gavutis M., Lata S., Lamken P., Mueller P., Piehler J.,
    Lateral ligand-receptor interactions on membranes studied by simultaneous fluorescence-interference detection(PDF)
    Biophys. J. 88 (2005) 4289-4302.
  • Piehler, J.,
    New methodologies for measuring protein interactions in vivo and in vitro, (PDF)
    Curr. Opin. Struct. Biol. 15 (2005) 4-14.
  • Lata, S., Piehler, J.,
    Stable and functional immobilization of histidine-tagged proteins via multivalent chelator head-groups on a molecular poly(ethylene glycol) brush, (PDF)
    Anal. Chem. 77 (2005) 1096 -1105.
  • Lamken, P., Lata, S., Gavutis, M., Piehler, J.,
    Ligand-induced assembling of the type I interferon receptor on supported lipid bilayers, (PDF)
    J. Mol. Biol. 341 (2004) 303-318.
  • Piehler, J., Schreiber G.,
    Free energy landscapes in protein-protein interactions,
    Handbook of Cell Signaling, edited by R. A. Bradshaw and E. A. Dennis, Elsevier (2003).
  • Roisman, L., Piehler, J., Trosset, J.-Y., Scheraga, H. and Schreiber, G.,
    Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking, (PDF)
    Proc. Natl. Acad. Sci. USA 98 (2001) 13231-36.
  • Piehler J., Schreiber G.,
    Fast transient cytokine-receptor interactions monitored in real-time by reflectometric interference spectroscopy, (PDF)
    Anal. Biochem. 289 (2001) 173-186.
  • Piehler J., Roisman L., Schreiber G.,
    New structural and functional aspects of the type I interferon-receptor interaction revealed by comprehensive mutational analysis of the binding interface, (PDF)
    J. Biol. Chem. 275 (2000) 40425-40433.
  • Busch K., Piehler J., Fromm H.,
    Plant succinic semialdehyde dehydrogenase: dissection of nucleotide binding by surface plasmon resonance and fluorescence spectroscopy, (PDF)
    Biochemistry 39 (2000) 10110-10117.
  • Piehler J., Brecht A., Valiokas R., Liedberg B. and Gauglitz G.,
    A high-density poly(ethylene glycol) polymer brush for immobilization on glass-type surfaces, (PDF)
    Biosens. Bioelectron. 15 (2000) 473-481.
  • Piehler J., Schreiber G.,
    Mutational and structural analysis of the binding interface between type I interferons and their receptor ifnar2, (PDF)
    J. Mol. Biol. 294 (1999) 223 - 237.
  • Piehler J., Schreiber G.,
    Biophysical analysis of the human type I interferon receptor ifnar2 expressed in E. coli with interferon alpha2, (PDF)
    J. Mol. Biol. 289 (1999) 57 - 67
  • Harris R.D., Luff B. J., Wilkinson J.S., Piehler J., Brecht A., Gauglitz G., Abuknesha R. A.,
    Integrated optical surface plasmon resonance immunosensor for simazine detection(PDF)
    Biosens. Bioelectron. 14 (1999) 377-386.
  • Piehler J., Brecht A., Hehl K., Gauglitz G.,
    Protein interactions in covalently attached dextran layers,
    Colloids Surf. B: Biointerfaces, 13 (1999) 325-336.
  • Gauglitz G., Piehler J., Bilitewski U.
    Affinity sensor systems, in: Biosensors in environmental monitoring,
    ed. by U. Bilitewski and A.Turner, Harwood Academic Publishers GmbH, 163-177.
  • Luff J., Wilkinson J. S., Piehler J., Hollenbach U., Ingenhoff J., Fabricius N.
    Integrated optical Mach-Zehnder biosensor
    IEEE Journal of Lightwave Technology 16 (1998) 583-592.
  • Schmitt H.-M., Brecht A., Piehler J., Gauglitz G.
    An integrated system for optical biomolecular interaction analysis, (PDF)
    Biosens. Bioelectron. 12 (1997) 809-816.
  • Piehler J., Maul C., Brecht A., Zerlin M., Thiericke R., Grabley S., Gauglitz G.
    Label-free monitoring of DNA-ligand interactions, (PDF)
    Anal. Biochem. 249 (1997) 94-102.
  • Piehler J., Brandenburg A., Brecht A., Wagner E., Gauglitz G.
    Characterisation of grating couplers for affinity based pesticide sensing, (PDF)
    Appl. Optics 36 (1997) 6554-6562.
  • Piehler J., Maul C., Brecht A., Zerlin M., Grabley S., Gauglitz G.
    Specific binding of low molecular weight ligands with direct optical detection, (PDF)
    Biosens. Bioelectron. 12 (1997) 531-538.
  • Drapp B., Piehler J., Luff B. J., Brecht A., Wilkinson J. S., Gauglitz G., Ingenhoff J.
    Integrated optical Mach-Zehnder Interferometers as Simazine Immunoprobes, (PDF)
    Sens. Actuators B 38-39 (1997) 277-282.
  • Piehler J., Brecht A., Giersch T., Kramer K. Hock B, Gauglitz G.
    Characterisation of monoclonal and recombinant antibodies for multi-analyte detection using direct optical transducers, (PDF)
    Sens. Actuators B 38-39 (1997) 432-437.
  • Piehler J., Brecht A., Giersch T., Hock B., Gauglitz G.
    Assessment of affinity constants by rapid solid phase detection of equilibrium binding in a flow system, (PDF)
    J. Immunol. Meth. 201 (1997) 189-206.
  • Mouvet C., Harris R. D., Maciag C., Luff B. J., Wilkinson J. S., Piehler J., Brecht A., Gauglitz G., Abuknesha R., Ismael G.
    Determination of siamzine in water samples by waveguide surface plasmon resonance,
    Anal. Chim. Acta 338 (1997) 109-117.
  • Piehler J., Brecht A., Geckeler K. E., Gauglitz G.
    Surface modification for direct immunoprobes, (PDF)
    Biosens. Bioelectron. 11 (1996) 579-590.
  • Piehler J., Brecht A., Gauglitz G.
    Affinity detection of low molecular weight analytes, (PDF)
    Anal. Chem. 68 (1996) 139-143.

In our young, expanding group we always have positions available for motivated students of Biology, Biochemistry, Chemistry, Physics and related subjects.

We can offer a spirited and committed scientific atmosphere in an interdisciplinary group jointly working on exciting topics of molecular cell biophysics.

State of the art technology in the field of molecular, structural and cell biology, protein and peptide biochemistry as well as optical spectroscopy and biophysics is available.

Students of different nationalities work in our research department, and thus, the language of all research seminars is English.

We are highly interested in international scientific exchange and thus we explicitly encourage foreign students and PhDs to apply for positions in our groups.

PhD Students

The doctoral students in the group have joined us from many different Universities in Europe and have studied Biochemistry, Biology or Chemistry. PhD-students are usually paid according to TVöD E13, or by fellowships from the DFG, which is in the same order of magnitude.
Apply for position

Postdoctoral Fellows

Typically, postdoctoral fellows should be successful in obtaining a fellowship supporting at least part of the time they spent in the group. Not all fellowships are open to all nationalities and therefore strategies have to be specifically devised. We will, however, be committed to help with these applications.
Apply for position

Graduate Students

Several departments encourage or even require students to spend some time in a research lab to acquire experimental skills. We regularly host such students, several of whom have returned later for diploma and/or doctoral work. Usually such stays last from 6 weeks to 4 months, and the students must have basic training in experimental biochemistry before coming. They would work under the guidance of an experienced doctoral student in an ongoing project. Please be aware such stays need to be arranged well in advance, and therefore contact us in due course.
Apply for position

Prof. Dr. Jacob Piehler
Department of Biology/Chemistry
Barbarastr. 11
49076 Osnabrück
Germany (Google Maps)

Travelling by Car:

Exit A30 at Hellern and follow signs towards the inner city. At the inner city ring, turn left and follow signs "Fachhochschule", "Universität Osnabrück, Standort Westerberg". Building 35-37 is located at the end of the Barbarastasse.

Travelling by Plane:

From Münster-Osnabrück airport (FMO) take the shuttle bus to the train station in Osnabrück. (Timetable). To reach us from the train station please refer to the "Travelling by Train" information.

Travelling by Train:

From the train station "Bussteig 1" take bus 21 to the stop "Hochschulen Westerberg" (Timetable). From there you can walk within 5 minutes to our institute, located in building 36. You will find us on the first floor, left corridor.