Research Area & Methods

Surface chemistry for biofunctionalization on graphene, Si-wafer, gold and glass
Nanostructured interfaces (quantum dots, Au nanoparticles, liposomes) for bioanalytics
Graphene induced energy transfer (GIET) for structural biology
Multiprotein assembly of Wnt signaling in mammalian cells and mesenchymal stem cells

Chemical modification of peptide, protein and polymer
Photo-lithography and soft-lithography
Label-free detection by reflectometry and localized surface plasmon resonance
Fluorescence spectroscopy and microscopy
Single molecule localization microscopy for superresolution imaging

Research Topics

Multimodal structural biology of membrane protein complexes on graphene
Graphene has been used as an ideal substrate of cryo-electron microscopy (Cryo-EM) and correlated light and electron microscopy (CLEM). Recent studies confirm graphene-induced energy transfer (GIET) is a novel spectroscopic ruler up to 30 nm with subnanometer resolution. Aim of this project is to establish graphene as a versatile platform for characterizing the structure and dynamics of membrane proteins by fluorescence spectroscopy and microscopy. Development of GIET in combination with Cryo-EM and CLEM will achieve a detailed structural picture of proteins in action.

Interfacing live cells on nanostructures for label-free detection
To exploit the much more characteristic refractive index dispersion in the mid-infrared (IR) regime, we have engineered three-dimensional IR-resonant silicon micropillar arrays (Si-MPAs) for protein sensing. Hierarchical nano- and microstructured design of Si-MPAs is fabricated by CMOS-compatible silicon-based microfabrication processes. Using this sensor platform, an optimized interrogation of surface protein binding is achieved using Fourier transform IR spectroscopy.

Manipulation of canonical Wnt signaling complexes
The canonical Wnt signalling pathway is a key regulatory hub in stem cell differentiation and embryonic development. Numerous biomolecules are involved in the formation of ‘Wnt-signalosome’, where liquid-liquid phase separations of proteins play important roles for spatiotemporal regulation the Wnt signaling. Aimed to dissect the molecular mechanism governing the assembly of Wnt signalosomes, we are developing protein micro/nano-patterning of living cells. Magnetogenetics tools are employed for manipulation of the canonical Wnt signaling.

Selected Publications

Research Articles

Flesch J., Bettenhausen M., Kazmierczak M., Klesse W. M., Skibitzki O., Psathaki O. E., Kurre R., Capellini G., Guha S., Schroeder T., Witzigmann B., You C., Piehler J. (2021) Three-Dimensional Interfacing of Cells with Hierarchical Silicon Nano/Microstructures for Midinfrared Interrogation of In Situ Captured Proteins. ACS Applied Materials & Interfaces, doi: 10.1021/acsami.0c22421.

Füllbrunn N., Li Z., Jorde L., Richter C. P., Kurre R., Langemeyer L., Yu C., Meyer C., Enderlein J., Ungermann C., Piehler J., You C. (2021) Nanoscopic anatomy of dynamic multi-protein complexes at membranes resolved by graphene-induced energy transfer. eLife 10, e62501,doi: 10.7554/eLife.62501.

Janda C. Y., Dang L. T., You C., Chang J., de Lau W., Zhong Z. A., Yan K. S., Marecic O., Siepe D., Li X., Moody J. D., Williams B. O., Clevers H., Piehler J., Baker D., Kuo C. J., Garcia K. C. (2017) Surrogate Wnt agonists that phenocopy canonical Wnt and beta-catenin signalling. Nature 545, 234-237,doi: 10.1038/nature22306.

You C., Marquez-Lago T. T., Richter C. P., Wilmes S., Moraga I., Garcia K. C., Leier A., Piehler J. (2016) Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling. Science advances 2, e1600452,doi: 10.1126/sciadv.1600452.

Wedeking T., Löchte S., Richter C. P., Bhagawati M., Piehler J., You C. (2015) Single Cell GFP-Trap Reveals Stoichiometry and Dynamics of Cytosolic Protein Complexes. Nano Letters 15, 3610-3615,doi: 10.1021/acs.nanolett.5b01153.

Book chapter & Reviews

Philippi M., Li Z., Bhagawati M., You C., "Single cell pulldown for characterization of protein complexes" in Handbook of Single Cell Technologies, F. Tseng, T. Santra, Eds. (Springer Nature, 2021), Chapter Spectrum analysis method, targets, imaging and applications. pp. 1-23. doi.org/10.1007/978-981-10-4857-9_43-1.

You C., Piehler J. (2016) Functional protein micropatterning for drug design and discovery. Expert Opinion on Drug Discovery 11, 105-119,doi: 10.1517/17460441.2016.1109625.

You C., Bhagawati M., Brecht A., Piehler J. (2009) Affinity capturing for targeting proteins into micro and nanostructures. Analytical and Bioanalytical Chemistry 393, 1563-1570,doi: 10.1007/s00216-008-2595-6.

People

Principal Investigator
Changjiang You, PhD
Senior Lecturer (Akad. Rat)

Education
1994-1998	BS in Chemistry, Sun-Yat-Sen University, Guangzhou, China
1998-2004	PhD, Chinese Academy of Sciences, Technical Institute of Physics and Chemistry, Beijing, China (PhD thesis in Photochemistry)

Research Experiences
2004-2005	CNRS postdoc fellow, CNRS8612 - Surface Chemistry & Faculty of Pharmaceutics, Paris-Sud University, Paris, France (Prof. Dr. Véronique Rosilio)
2006-2007	Postdoc, Department of Physics, Emory University, Atlanta, USA (Prof. Dr. Keith Berland)
2007-2010	Postdoc, Institute of Biochemistry, Goethe-University Frankfurt/Main, Frankfurt/Main, Germany (Prof. Dr. Jacob Piehler)

Positions
Since 2010	Senior Lecturer, Division of Biophysics, Department of Biology/Chemistry, University of Osnabrück
Since 2017	Principal Investigator, Center of Cellular Nanoanalytics (CellNanOs), University of Osnabrück

Fellowship and Awards
1995-1997	1^st grade outstanding student fellowships by Sun-Yat-Sen University, Guangzhou, China
1998	Recommended PhD candidate to the Chinese Academy of Sciences, Beijing, China
2004-2005	CNRS postdoctoral fellowship, Paris, France
2016-2017	Young investigator start-up funding by SFB 944, Osnabrück, Germany

Institutional Responsibilities
Since 2016	Examiner of Prüfungsausschusses Biologie, Department of Biology, University of Osnabrück
Since 2016	Lecturer of international summer school, Department of Biology, University of Osnabrück
Since 2019	Committee member of graduate school initative Nano/Bio, Center of Cellular Nanoanalytics (CellNanOs), University of Osnabrück

Teaching
Since 2011	Erweiterungsmodul Biophysik: Zelluläre Biophysik – Konzepte und Methoden (BIO-MM-BP)
Since 2016	Mastermodul Biophysik: Biological Spectroscopy and Microscopy (BIO-MM-BP)
Since 2020	Mastermodul Biophysik: NanoBioPhysics (BIO-MM-BP)

Postdoctors
Michael Philippi
Surface biofunctionalizaiton, nanopatterning of signaling complex

PhD Students
Julia Flesch (joint supervision with Prof. Jacob Piehler)
Interfacing live cells with nanostructures, LSPR detection
Marie Kappen (joint supervision with Prof. Jacob Piehler)
Bio-functional nanoparticles, Magnetogenetics in live cells
Lara Jorde (joint supervision with Prof. Arne Möller)
Lipid membrane structures on graphene

Master Students
Arthur Felker
Nanopatterning on graphene

Visiting Scientists
Hailong Wang (Beijing Xunshi Rongchuang Tech Co. Ltd.)

Collaborations
Veronique Rosilio (University Paris-Saclay, France)
Maxime Dahan (Insitute Curie, France)
K. Christopher Garcia (Stanford University, USA)
Hong Wang (North Carolina State University, USA)
Dayong Wu (TICP, CAS, Beijing, China)