B CUBE Junior Research Group
'Bioresponsive Materials'

B CUBE's first Junior Research Group is led by Dr. Yixin Zhang.

He received his PhD in biochemistry at University of Halle at the Max Planck Research Unit for Enzymology of Protein Folding where he continued working at a post doc until 2004. He then joined the Institute of Pharmaceutical Sciences at ETH Zürich as scientific staff in the department of Chemistry and Applied Biosciences. In 2008, he was selected by BMBF as junior research group leader for ZIK B CUBE. Contact details

Our research interests are:

 

New functions for bioactive molecules and drugs

We design and synthesize derivatives of bioactive compounds, to create new functions such as:
1) Responsiveness to light irradiation.
2) High specificity and affinity to target protein.
3) Improved pharmacokinetics.

The photo-responsive derivative of immunosuppressive drug cyclosporin A allows us to tune the immune system with IR light.

 

Drug discovery using chemical libraries with screening and selection

Nature develop specific binding molecules (e.g. antibody) using selection, while human discover small molecule drugs using screening. The emerging field of DNA encoded chemical library allows us to perform selection of small molecule compounds. We combine both technologies, to illustrate their advantages and disadvantages, and to discover high specific inhibitors against proteins of medicinal interest.

Selection vs Screening

 

Self-assembled biomaterials for cell culture

The biology of cells are often associated with their particular niches. We build up polymer matrices with defined chemical composition to mimic their environment under physiological and pathological conditions, to supply nutrition, to provide signaling, to create polarized conditions, and to, ultimately, allow the cells to develop and migrate.

 

Lab members

  Lab statue and major research interest Education  
Boden, Annett PhD student. Light switchable polymer matrices and drug molecules M.S. TU Dresden  
Ernyei, Aliz Scientist. Experimental validation of drug targeting predicted by virtual screening. Diploma, Budapest University, Hungary  
Herrmann, Jana Scientist. Protein display & enzymology. Ph.D. Technical University of Munich, Germany  
Hofmann, Ulrike Technical assistant. Peptide synthesis. Chemistry technician  
Krishnan, Swati Student. Self-assembling hydrogel B.E. Visveswariah Technological University, India.  
Lin, Weilin PhD student. Combinatorial chemical library of immunosuppressive compounds. M.S. Beijing Normal University, China  
Murawala, Priyanka Scientist. Cellular assays for immunosuppressive and anti-cancer compounds. Ph.D. Pune University India  
Thomas, Alvin PhD student. Protein engineering and single molecule fluorescence dye. M.S. University of Barcelona, Spain  
Thompson, Mike PhD student. Light switchable hydrogel. B.S. University of Florida, USA  
Uzunova, Veselina Scientist. Combinatorial chemical library & cell reprogramming. Ph.D. University of Houston, USA  
Wieduwild, Robert PhD student. DNA encoded chemical library and self-assembled hydrogel. Diploma, Halle University, Germany  
Zhang, Yixin Group leader. Macromolecule chemical modifications. Ph.D. Max Planck Research Unit, Halle, Germany  

Selected publications

  • F. Erdmann, Y. Zhang "Reversible photoswitching of protein function." Mol. Biosyst. (2010) 6, 2103.
  • Y. Zhang, F. Erdmann, G. Fischer "Augmented Photoswitching Modulates Immune Signaling" Nature Chemical Biology, (2009) 5, 724.
  • L. Mannocci, Y. Zhang, J. Scheuermann, M. Leimbacher, G. Bellis, E. Rizzi, C. Dumelin, S. Melkko, Dario Neri “High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries” PNAS (2008) 46, 17670.
  • S. Melkko, Y. Zhang, C. E. Dumelin, J. Scheuermann, D. Neri “Isolation of High-Affinity Trypsin Inhibitors from a DNA-Encoded Chemical Library” Angew. Chem. (2007) 46, 4671.
  • Y. Zhang, F. Erdmann, R. Baumgrass, M. Schutkowski, G. Fischer “Unexpected Side Chain Effects at Residue 8 of Cyclosporin A Derivatives Allow Photoswitching of Immunosuppression” J. Biol. Chem. (2005) 4842.
  • R. Baumgrass, Y. Zhang, F. Erdmann, A. Thiel, M. Weiwad, A. Radbruch, G. Fischer. “Substitution in Position 3 of Cyclosporin A Abolishes the Cyclophilin-mediated Gain-of-function Mechanism but Not Immunosuppression” J. Biol. Chem. (2004) 2470
  • Y. Zhang, R. Baumgrass, M. Schutkowski, G. Fischer “Branches on the alpha-C Atom of Cyclosporin A Residue 3 Result in Direct Calcineurin Inhibition and Rapid Cyclophilin 18 Binding.” ChemBioChem (2004) 5, 1169.
  • Y. Zhang, S. Fussel, U. Reimer, M. Schutkowski, G. Fischer “Substrate-based design of reversible Pin1 inhibitors.” Biochemistry (2002) 41, 11868.