Research Interests

Our research is contributing to a recently emerged interdisciplinary area of Nanobiotechnology. In nature, innumerous highly functional nanomachines are precisely self-assembled from different biomacromolecules by means of non-covalent interactions. These sophisticated systems impressively demonstrate the power of programmed self-recognition of biomacromolecules. Inspired by the brilliant systems in nature, research on Nanobiotechnology exploits the nanostructuring and nanofabrication of active biomacromolecules and studies the interface between biomolecules and nanotechnology. Nanobiotechnology is envisioned to assist understanding substantial new insights into how biological systems function, and in turn lead to the design of entirely new classes of micro- and nanofabricated devices and machines.

In particular, our research concerns the development of hybrid nanomaterials self-assembled from proteins, nucleic acids and inorganic nanoparticles. In addition to fundamental studies on protein modifications and self-assembly methodologies, we particularly focus on their applications for nanomedicine, theranostic, biocatalysis and stimuli responsive materials.

 

1. Controlled fabrication of protein suprastructures guided by oligonucleotides

Synthetic DNAs have proved to be extraordinarily useful building blocks for nanostructuring. Due to the highly specific complementary interactions between designable nucleic acid strains and the great mechanical rigidity of the short double helices, these genetic materials have been rapidly developed in the last few decades for nanostructuring from two-dimensional to three-dimensional structures, and even smart nanomachines. Integration of these fantastic DNA nanodevices with the highly sophisticated biofunctions provided by proteins pave a way to a new area of functional nanomachines. Our research covers from protein-DNA nano-conjugates to 1D and 2D protein patterning and 3D smart protein-DNA nanomachines.

 

2. Protein copolymer based nanodevices for biomedical application

Existing small molecular therapeutics often elicit severe side effects due to the systemic distribution of cytostatic drugs. To improve therapeutic efficacy and reduce toxicity, developing of efficient drug delivery platforms is attracting an exponentially growing attention in the last decades. Proteins are particularly attractive materials for developing drug delivery systems since they are originated from biological systems and can be easily degraded by endogenous enzymes, therefore they have reduced toxicity risk. However, using native protein to construct drug delivery platforms is limited by the variations of proteins and tedious modifications. We have developed a comprehensive and highly versatile approach to prepare protein based polypeptide copolymers (PbPs) from natural proteins with distinct molecular weights, chain lengths, ordered secondary structural elements and high numbers of functional groups. To achieve such copolymers, a novel method has been established to unfold the globular structure of native proteins under controlled condition and in situ stabilize the polypeptide backbone by grafting polyethylene(oxide) (PEO) chains to avoid precipitation. Such PbPs possess the benefits of protein based materials, such as monodisperse chain length, ordered secondary structures, biocompatibility and biodegradability. In addition, their unfolded backbone enables more flexible modifications and opens up further possibilities to re-assemble the backbone under desired conditions. We built up various unique hybrid materials from these copolymers for a broad range of biomedical applications, such as patterned biofilms, environmental responsive hydrogel matrix, multi-stimuli responsive drug delivery systems, efficient gene delivery carriers as well as multifunctional nanomicelles for spontaneously MRI imaging and therapy.

Representative publications:

Yuzhou Wu, Goutam Pramanik, Klaus Eisele, Tanja Weil. Convenient approach to polypeptide copolymers derived from native proteins. Biomacromolecules, 2012, 13(6):1890-1898

Yuzhou Wu, Susann Ihme, Michaela Feuring-Buske, Seah Ling Kuan, Klaus Eisele, Markus Lamla, Yanran Wang, Christian Buske, and Tanja Weil. A core-shell albumin copolymer nanotransporter for high capacity loading and two-step release of doxorubicin with enhanced anti-leukemia activity. Adv. Healthcare Mater., 2013, 2(6):884-894.

Seah Ling Kuan, Yuzhou Wu, Tanja Weil, Precision Biopolymers from Protein Precursors for Biomedical Applications. Macromol. Rapid Commun., 2013, 34(5):380-392.

Seah Ling Kuan, Yuzhou Wu, Tanja Weil, Precision Biopolymers from Protein Precursors for Biomedical Applications. Macromol. Rapid Commun., 2013, 34(5):380-392

3. Interface between proteins and inorganic nanoparticles

Nanoparticles are widely used in biological systems for labeling, imaging, drug delivery and therapy. Although remarkable advantages have been revealed by using nanoparticles, the issue of toxicity associated with the most nanopariticles is the major limitation for this technique. Decoration of nanoparticle surface by various proteins has been proved as an effective strategy to improve the biocompatibility of nanoparticles and also provide further functionalities. We are interested in studying the coating of different nanoparticle, e.g. quantum dots, gold nanoparticles, nanodiamonds and silica nanoparticles with multifunctional protein shell for biomedical applications. In particularly, we have developed a highly stable and biocompatible albumin-copolymer coated quantum dots system. This system exhibit significant environmental sensitive optical properties, and can also be used as gene delivery carrier allowing in vivo monitoring of gene delivery process.

 

Representative publications:

Yuzhou Wu*, Fedor Jelezko, Martin Plenio, Tanja Weil*, Diamond Quantum Sensing in Biology, Angew. Chem. Int. Ed., 2015, just accepted.

Yuzhou Wu*, Anna Ermakova, Weina Liu, Goutam Pramanik, Minh Vu, Andrea Kurz, Liam McGuinness, Boris Naydenov, Susanne Hafner, Rolf Reuter, Joerg Wrachtrup, Dominique Böcking, Junichi Isoya, Thomas Simmet, Fedor Jelezko*, Tanja Weil*, Programmable Biopolymers for Advancing Biomedical Applications of Fluorescent Nanodiamonds, Adv. Funct. Mater., 2015, DOI: 10.1002/adfm.201502704.

Yuzhou Wu, Sabyasachi Chakrabortty, Radu A. Gropeanu,Joerg Wilhelmi,Yang Xu, Kai Shih Er, Seah Ling Kuan, Kaloian Koynov, Yinthai Chan and Tanja Weil. pH-Responsive Quantum Dots via an Albumin Polymer Surface Coating. J. Am. Chem. Soc., 2010, 132(14):5012-5014.

Yuzhou Wu, Klaus Eisele, Mikheil Doroshenko, Gerardo Algara-Siller, Ute Kaiser, Kaloian Koynov, Tanja Weil, A Quantum Dot Photoswitch for DNA Detection, Gene Transfection, and Live-Cell Imaging. Small, 2012, 8 (22): 3465–3475.

Group Members:

Sabyasachi Chakrabortty, Postdoc

Felix Boldt, PhD Student

Weina Liu, PhD Student

Yu Tokura, PhD Student

Jasmina Gacanin, PhD Student

Made Budiarta, Masters Student

Past Members

Johanna Quambusch, Masters Student

Viktoria Mikhalevich, Master Student

Tammy Tran, Master Student

Yanran Wang, Master Student

Ana Chaves, Erasmus Student

Claudia Tippel, Bachelor Student

Short CV:

Education

06/2010-05/2013     Ph.D. (Summa Cum Laude), Ulm University (Supervisor: Prof. Tanja Weil).

08/2008-06/2010     M.Sc., National University of Singapore (Supervisor: Prof. Tanja Weil).

09/2004-07/2008     B.Sc., Zhejiang University, China.

08/2006-07/2007     Exchange Student, Hong Kong University, Hong Kong, China.

 

Research Experience

06/2013-present      Group leader in Institute of Organic Chemistry III, Ulm University, Germany.

04/2012-04/2013     Research scientist under Prof. Klaus Müllen (Max-Planck Institute for Polymer Research) and Prof. Heiko Luhmann (Mainz University).

06/2010- 03/2012    Research scientist under Prof. Tanja Weil. (Ulm University).

01/2009-06/2010     Master’s thesis under Prof. Tanja Weil. (National University of Singapore).

11/2008-01/2009     Research training under Prof. Chu Young Kim. (National University of Singapore).

08/2008-11/2008     Research training under Prof. Shao Qin Yao. (National University of Singapore).

01/2008-07/2008     Bachelor thesis under A/P. Ming Lei. (Zhejiang University).

08/2006-07/2007     Research training in Prof. Patrick Toy´s lab. (Hong Kong University).

02/2006-08/2006     Research training in Prof. Xian Huang´s lab. (Zhejiang University).

Funding

2014-2017: Protein-DNA Hybrid Hydrogels as Sustainable Materials for Tissue Engineering (BioMatS-15)

Prizes and Scholarships

01/2015 Forschungsboni of the Ulmer Universitätsgesellschaft

07/2014 Promotionspreis of the Ulmer Universitätsgesellschaft

06/2013  Finalist of 2013 Reaxys PhD Prize.

05/2013  Selected for the Final Round of the Lanxess Talent award 2013 (Lanxess Germany GmbH and the Research Institute for Interactive Materials at Aachen University).

04/2013  Chinese Government Award for Outstanding Self-Financed Students Abroad 2012 (China Scholarship Council, China).

2008-2010  Research Scholarship (National University of Singapore, Singapore).

07/2008  The Excellent Graduate of Zhejing Province (Educational Office of Zhejiang Province, China).

11/2007  The National Scholarship (Ministry of Education, China).

2006-2007  Fung Scholarship (Fung Foundation, Hong Kong).

Publications:

1. Yuzhou Wu*, Fedor Jelezko, Martin Plenio, Tanja Weil*, Diamond Quantum Sensing in Biology, Angew. Chem. Int. Ed., 2015, just accepted.
2. Yuzhou Wu*, Anna Ermakova, Weina Liu, Goutam Pramanik, Minh Vu, Andrea Kurz, Liam McGuinness, Boris Naydenov, Susanne Hafner, Rolf Reuter, Joerg Wrachtrup, Dominique Böcking, Junichi Isoya, Thomas Simmet, Fedor Jelezko*, Tanja Weil*, Programmable Biopolymers for Advancing Biomedical Applications of Fluorescent Nanodiamonds, Adv. Funct. Mater., 2015, DOI: 10.1002/adfm.201502704.
3. Tao Zhang, Andre Neumann, Jessica Lindlau, Yuzhou Wu, Goutam Pramanik, Boris Naydenov, Fedor Jelezko, Florian Schüder, Sebastian Huber, Marinus Huber, Florian Stehr, Alexander Högele*, Tanja Weil* and Tim Liedl*, DNA-based self-assembly of fluorescent nanodiamonds, J. Am. Chem. Soc., 2015, DOI: 10.1021/jacs.5b04857.
4.  Yuzhou Wu, David Yuen Wah Ng, Seah Ling Kuan, Tanja Weil*, “Protein-Polymer Therapeutics – A Macromolecular Perspective”, Biomaterials Science, 2015, 3, 214-230.
5. René Stangenberg#, Yuzhou Wu#, Seah Ling Kuan, Dennis Kurzbach, Dariush Hinderberger, Jana Hedrich, Malin Insa Preiß, Heiko J. Luhmann, Tanja Weil* and Klaus Müllen*, “A Polyphenylene Dendrimer Drug Transporter with Precisely Positioned Amphiphilic Surface Patches”, Adv. Healthcare Mater., 2015, 4, 377-384. (#Shared first authorship).
6. Tao Wang, Yuzhou Wu, Seah Ling Kuan, Oliver Dumele, Markus Lamla, David Y. W. Ng, Matthias Arzt, Jessica Thomas, Jan. O. Mueller, Christopher Barner-Kowollik*, Tanja Weil*, A Disulfide Intercalator Toolbox for Site-Directed Polypeptide Modification, Chemistry – a European Journal, 2015, 21, 228-238.

7.     Tao Wang, Natalia Zabarska, Yuzhou Wu, MarkusLamla, Stephan Fischer, Katharina Monczak, David Y. W.Ng,* SvenRau* and TanjaWeil*, Receptor Selective Ruthenium-Somatostatin Photosensitizer for Cancer Targeted Photodynamic Applications, Chem. Commun. 2015, 51, 12552-12555.

8.     Yuzhou Wu*, Chuang Li, Felix Boldt, Christina Förtsch, Holger Barth, Yanran Wang, Seah Ling Kuan, Thuy Tam Tran, Viktoria Mikhalevich, Zhongqiang Yang, Dongsheng Liu*, Tanja Weil*, “Programmable protein–DNA hybrid hydrogels for the immobilization and release of functional proteins”, Chem. Comm., 2014, 50, 14620-14622.

9.     David Yuen Wah Ng#, Yuzhou Wu#, Seah Ling Kuan and Tanja Weil*, “Programming Supramolecular Biohybrids as Precision Therapeutics”, Acc. Chem. Res., 2014, 47, 3471-3480. (#Shared first authorship).

10.  Chuang Li, Ping Chen, Yu Shao, Xu Zhou, Yuzhou Wu, Zhongqiang Yang, Zhibo Li, Tanja Weil, Dongsheng Liu*, “A writable polypeptide-DNA hydrogel with rationally designed multi-modification sites”, Small, 2014, 11, 1138-1143.

11.  Tao Wang, David Y. W. Ng, Yuzhou Wu, Jessica Thomas, Thuy TamTran and Tanja Weil*. “Bis-sulfide bioconjugates for glutathione triggered tumor responsive drug release” Chem. Commun., 2014, 50, 1116-1118.

12. David Y. W. Ng, Matthias Arzt, Yuzhou Wu, Seah Ling Kuan, Markus Lamla, Tanja Weil*. “Constructing Hybrid Protein Zymogens through Protective Dendritic Assembly” Angew. Chem. Int. Ed. 2014, 53, 324-328.
13. Christoph Meier, Yuzhou Wu, Goutam Pramanik, Tanja Weil*. “Self-​Assembly of High Molecular Weight Polypeptide Copolymers Studied via Diffusion Limited Aggregation” Biomacromolecules, 2014, 15, 219-227.
14. David Yuen Wah Ng, Jörg Fahrer, Yuzhou Wu, Klaus Eisele, Seah Ling Kuan, Holger Barth*, Tanja Weil*. “Efficient Delivery of p53 and Cytochrome C by Supramolecular Assembly of a Dendritic Multi-Domain Delivery System” Adv. Healthcare Mater. 2014, 2, 1620-1629.
15. Yuzhou Wu, Susann Ihme, Michaela Feuring-Buske, Seah Ling Kuan, Klaus Eisele, Markus Lamla, Yanran Wang, Christian Buske, and Tanja Weil*. “A Core-shell Albumin Copolymer Nanotransporter for High Capacity Loading and Two-step Release of Doxorubicin with Enhanced Anti-leukemia Activity” Adv. Healthcare Mater., 2013, 2, 884.

16.  Diego Pesce#, Yuzhou Wu#, Anke Kolbe, Tanja Weil* and Andreas Herrmann*. “Enhancing Cellular Uptake of GFP via Unfolded Supercharged Protein Tags” Biomaterials, 2013, 34, 4360. (#Shared first authorship).

17. Seah Ling Kuan, David Y. W. Ng, Yuzhou Wu, Christina Förtsch, Holger Barth, Mikheil Doroshenko, Kaloian Koynov, Christoph Meier, Tanja Weil*. J. Am. Chem. Soc. 2013, 135, 17254.
18. Jana Hedrich, Yuzhou Wu, Seah Ling Kuan, Frauke Kuehn, Eweline Pietrowski, Mike Sahl, Sandra Muth, Klaus Müllen, Heiko J. Luhmann, Tanja Weil, Manfred Schmidt. “Polymer Complexes in Biological Applications” Adv. Polym. Sci. 2013, doi: 10.1007/12_2013_229. (Book Chapter).
19. Tao Wang, Anne Pfisterer, Seah Ling Kuan, Yuzhou Wu, Oliver Dumele, Markus Lamla, Klaus Müllen and Tanja Weil*. “A Versatile and Orthogonal Approach for the Cross-Conjugation of DNA, Proteins and Peptides via the pH Switch” Chem. Sci., 2013, 4, 1889-1894.
20. Seah Ling Kuan, Yuzhou Wu, Tanja Weil*. “Precision Biopolymers from Protein Precursors for Biomedical Applications” Macromol Rapid Commun., 2013, 34, 380.

21.  Seah Ling Kuan, Bettina Stöckle, David Y.W. Ng, Yuzhou Wu, Mikheil Doroshenko, Jörg Reichenwallner, Kaloian Koynov, Dariush Hinderberger, Klaus Müllen and Tanja Weil*. “Dendronized Albumin Biohybrids as Efficient Core-Shell Doxorubicin Delivery Systems” Biomacromolecules, 2013, 14 (2): 367–376.

22. Yuzhou Wu, Klaus Eisele, Mikheil Doroshenko, Gerardo Algara-Siller, Ute Kaiser, Kaloian Koynov, Tanja Weil*. “A Quantum Dot Photoswitch for DNA Detection, Gene Transfection, and Live-Cell Imaging” Small, 2012, 8(22): 3465–3475. (Cover article)
23. Yuzhou Wu, Goutam Pramanik, Klaus Eisele, Tanja Weil*. “Convenient Approach to Polypeptide Copolymers Derived from Native Proteins” Biomacromolecules, 2012, 13(6):1890-1898.
24. Yuzhou Wu, Tao Wang, David Y.W. Ng, Tanja Weil*. “Multifunctional Polypeptide-PEO Nanoreactors via the Hydrophobic Switch” Macromol. Rapid Commun., 2012, 33(17):1474-1481.
25. Yuzhou Wu, Tanja Weil*. “An Efficient Approach for Preparing Giant Polypeptide Triblock Copolymers by Protein Dimerization” Macromol. Rapid Commun., 2012, 33(15):1304-1309.
26. Yuzhou Wu, Kai Shih Er, Arvind Ramanathan, Subhash Vasudevan, Tanja Weil*. “Nano-sized Albumin-copolymer Micelles for Efficient Doxorubicin Delivery” Biointerphases. 2012, 7(1-4):5.
27. Yasar Akdogan, Yuzhou Wu, Klaus Eisele, Manuela Schaz, Tanja Weil* and Dariush Hinderberger*.“Host-Guest Interactions in Polycationic Human Serum Albumin Bioconjugates” Soft Matter, 2012, 8(43): 11106-11114.
28. Tanja Weil, Goutam Pramanik, Yuzhou Wu. Protein-based copolymers for bioimaging and drug delivery applications. Polymer Preprints (American Chemical Society, Division of Polymer Chemistry), 2011, 52(1): no page given.
29. Yuzhou Wu, Sabyasachi Chakrabortty, Radu A. Gropeanu, Joerg Wilhelmi, Yang Xu, Kai Shih Er, Seah Ling Kuan, Kaloian Koynov, Yinthai Chan* and Tanja Weil*. “pH-Responsive Quantum Dots via an Albumin Polymer Surface Coating” J. Am. Chem. Soc., 2010, 132(14):5012-5014.
30. Yuzhou Wu, Tanja Weil. Multifunctional protein- hybrid and its applications in quantum dot coatings. Polymer Preprints (American Chemical Society, Division of Polymer Chemistry), 2010, 51(1): 786-787.
31. Yuguang Wang, Xian Huang*, Yuzhou Wu. “An Efficient Route to Vinyl Substituted Oxadiazoles and Triazoles using Phenylselanyl Derivatives as Precursor” Tetrahedron, 2007, 63(33):7866-7873.

 

 

Presentations at International Conferences:

1.         Y. Wu, G. Pramanik, K. Eisele, T. Weil. Precision Polypeptides Derived from Native Proteins for Biomedical Applications. Oral presentation, Belgian-German (Macro) Molecular Meeting, Houffalize, Belgium, Dec. 3-4th, 2012.

2.         Y. Wu, G. Pramanik, K. Eisele, T. Weil. A Multifunctional Protein Derived Polypeptide Copolymer and Its Applications. Poster presentation, EMBO Conference Series: Chemical Biology, Heidelberg, Germany, Sep. 26-29th, 2012.

3.         Y. Wu, T. Weil. Multifunctional Protein-hybrid and its Applications in Quantum Dot Coatings. Abstracts of Papers (Oral presentation), 239th ACS National Meeting, San Francisco, CA, United States, March 21-25th, 2010.

4.         Y. Wu, T. Weil. A Multifunctional Denatured Protein Based Polymer Material and Its Applications in Bioimaging and Drug Delivery. Oral presentation, Tag der Organischen Chemie (TOCUS), Stuttgart, Germany, Oct 15th, 2010.

5.         Y. Wu, T. Weil. Ph-Responsive Quantum Dots Via a Novel Protein-Polymer Coating. Oral presentation, 6th Singapore International Chemical Conference (SICC-6), Singapore, Dec 15-18th, 2009.

6.         Y. Wu, T. Weil. Botulinum Neurotoxin: from Inhibitor Design to Drug Delivery, Oral Presentation, 1st Singapore-Hong Kong Bilateral Graduate Student Congress in Chemical Sciences, Singapore, May 28-30th, 2009.

7.         T. Weil, S. L. Kuan, Y. Wu, Dendritic and Protein-based Nanocarriers. Poster presentation, NUS-SNU Joint Symposium: Frontiers in Fundamental and Applied Chemistry, Seoul, Korea, Feb 2009.