Dr. Bernd Wollscheid

 

Main Goals, Keywords

Dr. Bernd Wollscheid is heading the NCCR Neuro Center for Proteomics and a research group focusing on the detection and functional characterization of cell surface proteins upon perturbation of the nervous system as predictive markers of disease.

Quantitative Proteomics, Cell surface capturing (CSC), Neuroimmunology, Lymphoma, SISYPHUS Proteomics database, NCCR Neuro Center for Proteomics

Group Members

1 group leader, 2 PhD students, 1 project/lab manager

Previous and Current Research

The molecular composition and dynamic organization of the plasma membrane (PM) determines how a cell can interact with its environment at any given moment. Cell surface proteins are crucial for cell-cell communication, interaction with pathogens, binding of chemical messengers, and responding to environmental perturbations. Alterations in the PM protein composition, as a result of a disease may well define phenotypic and functional differences between normal, and for example tumour cells. Cell surface proteins can be markers of disease and are potential targets for pharmaceutical intervention. The goals of our research group are:

▪ To develop new methodologies for the specific labeling of proteins residing in the plasma membrane

▪ To capture, analyze and predict dynamic cell surface processes

▪ To establish maps of cell surface protein networks in order to identify differentiation marker patterns as therapeutic target groups towards predictive and preventive medicine

▪ To decipher specific ligand-receptor interactions on the cell surface

In order to achieve these goals, we are utilizing state-of-the-art quantitative proteomic tools in combination with fluorescence activated cell sorting technology, molecular imaging techniques and bioinformatic tools.

Currently, we are focusing on studying cell surface protein networks and receptor-ligand interactions in
primary immune cells in collaboration with the ETH Zurich Institute for Integrative Biology (M.Kopf) and the Children University Hospital Zurich (JP. Bourquin) and in primary neuronal cells (including stem cells) in collaboration with various groups within the NCCR Neuro (L. Sommer, R.Nitsch, M.Schwab, M.Weller).

Further, our group investigates cell surface protein expression changes upon pathogen entry into human cells within the InfectX project and works on the identification of cell surfac proteins relevant in drosophila melanogaster development within the WingX project.

Cell Surface Proteins identified via the in-house developed CSC (Cell Surface Capturing) technology and quantified with label (SILAC, iTRAQ, ICAT) and label-free (Superhirn, CORRA) quantitation methodologies are imported, annotated and integrated into functional protein networks by using the SisyphusDB. The Sisyphus Proteomics Database is a Cell Surface Peptide/Protein Atlas and set of tools developed in-house to gain insights into the functional implications of proteins in the plasma membrane.

Interesting candidates, and in particular, differentiation marker candidates are selected for subsequent validation and further functional characterization. The ultimate goal is to generate antibodies against these candidate proteins by using a new strategy which we recently developed (Patent pending) and to validate results obtained from cell populations on the single cell level using a combination of FACS (Fluorescence activated cell sorting), real-time, live cell confocal microscopy (Light Imaging Center, ETH Zurich) and automated RNAi screening (L.Pelkmanns, IMSB).

The NCCR Neuro Center for Proteomics at the Institute of Molecular Systems Biology allows neurobiologists to gain access to the methodologies of functional proteomics and provide a link to the research network in systems biology.
One of the objectives of the Center is to coordinate proteomic experiments and facilitates the use, maintenance and distribution of state of the art proteomic tools. The center offers support and expertise to other groups of the NCCR Neuro and provides educational programs, such as a proteomics software course. The center started its operation in April 2006.

Future Projects

• A new platform for the proteomic identification of malignant lymphoma cell membrane proteins as predictive markers of disease and therapeutic response
• Various projects in collaboration with members of the NCCR Neuro (Suter, Sommer, Relvas, Becher, Buch, Schwab, Nitsch, Fontana, Mansuy)

Please contact me (wollscheid@imsb.biol.ethz.ch) directly for details about these projects.

Techniques and Equipment

Our group is tightly integrated in the Institute for Molecular Systems Biology (IMSB), the NCCR Neuro and the Swiss Systems Biology initiative SystemsX. The ETH Zurich, Hönggerberg campus offers state-of-the art facilities for quantitative proteomics, computational analysis of large datasets, advanced light and electron microscopy, high-throughput, image-based RNAi and chemical compound screening.

Selected Publications

• Hofmann, A., Gerrits, B., Schmidt, A., Bock, T., Bausch-Fluck, D., Aebersold, R., Wollscheid, B. Proteomic cell surface phenotyping of differentiating acute myeloid leukemia cells. Blood. Jun 22 (2010) MEDLINE
• Wollscheid, B., Bausch-Fluck, D., Henderson, C., O'Brien, R., Schiess, R., Aebersold, R., Watts, J. Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotech. Apr; 27(4) (2009) MEDLINE
• Gupta, N., Wollscheid, B., Watts, J.D., Scheer, B., Aebersold, R., DeFranco, A.L. Quantitative proteomic analysis of B cell lipid rafts reveals that ezrin regulates antigen receptor-mediated lipid raft dynamics. Nature Immunology Nature Immunology. Jun7 (6) (2006) MEDLINE

Funding

NCCR Neuro

URL

www.imsb.ethz.ch/

www.imsb.ethz.ch/researchgroup/wbernd