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Welcome to the Wollscheid lab

Molecular Health

Decoding the extracellular Interactome
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Wollscheid lab

Molecular Health and Surfaceome Research

"If a cell surface molecule such as the B cell receptor would have the size of a human being, then the cell surface of a B cell would have roughly the size of three times NYC Central Park."

How many people/proteins/proteoforms reside in this space ("Surfaceome")? Similar to humans, proteins don't act alone. Function is encoded in dynamic protein-protein interactions. How are these proteoforms organized in signaling islands/networks in order to fulfill specific cellular functions ("Interactome")? What are the ligands interacting with the surfaceome to communicate information from other cells & tissues in the body? What goes wrong in these signaling islands if we get sick? Check out the baseball fields: A baseball field in the park would be one of those functional interaction islands upon which proteins – the players – group themselves for a particular cellular function – in this case, the baseball game. If the players leave the field, they lose their ability to function in this way. It's all about baseball & functional nanoscale organization of the surfaceome!

"Surfaceome nanoscale organization and extracellular interaction networks"
D. Bausch-Fluck, E. S. Milani, B. Wollscheid
Current Opinion in Chemical Biology (2019)

Our LUX-MS Technology

"With this technology called LUX-​MS, the researchers can determine with nanometer-​scale precision how proteins integrate into an organisation on the cell surface – in other words, which proteins are in proximity to each other." Harnessing the organisation of the cell surface (ETH News 02.12.2021 by Fabio Bergamin)
"Light-mediated discovery of surfaceome nanoscale organization and inter-cellular receptor interaction networks"
Nature Communications, 2021

Strategy

Measure. Integrate. Analyze. Validate.

The goal of the Wollscheid laboratory is to functionally understand the cellular surfaceome and its signaling islands as a complex information gateway connecting the intracellular to the extracellular interactome. We develop and apply next generation technologies at the interface of biology, chemistry, medicine and bioinformatics to generate unprecedented data to establish the surfaceome proteotype and its signaling interaction network. This digital proteotype data layer provides the basis for generating qualitative and quantitative surfaceome models explaining how molecular nanoscale organization influences cellular signaling and biological function.

Measure

Based on a specific biomedical question we measure millions of spectra derived from biospecimen using mass spectrometry.

Integrate

Using complex bioinformatic pipelines & statistical models we integrate the data and establish the proteotype of a biospecimen.

Analyze

We analyze the spatiotemporal dynamics of the biological system/proteotype under perturbation and generate hypotheses in order to explain the phenotype and molecular processes involved.

Validate

Using a variety of Systems Biology technologies we validate our findings and turn raw data into new biological insights & basic knowledge on how cells communicate.

Technology & Resources

Technologies & Resources empowering surfaceome research.

The Wollscheid lab developed a set of key Technologies & Resources which not only enable quantitative surfaceome discovery, but also the elucidation of functional protein-protein interactions. Life depends on interactions. The same holds true on the molecular level. Understanding molecular interaction networks is a prerequisite to understand basic biology and in turn, human health.

Surfaceome Screening

CSC Technology

Cell Surface Capture (CSC) technology enables qualitative & quantitative surfaceome discovery in order to phenotype cells without antibodies.

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Surfaceome Interactome Screening

TRICEPS-based LRC Technology

TRICEPS/HATRIC-based Ligand Receptor Capture (LRC) technology enables the identification of receptors for orphan ligands on living cells in order to deconvolute complex ligand receptor interactions. Technology patented by ETH licensed to dual systems.

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Intercellular Surfaceome Screening

LUX-MS Technology

LUX-MS enables the light-mediated proximity detection of cell surface signaling island & neighborhoods on living cells.

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Surfaceome KnowledgeBase

Cell Surface Protein Atlas

The Cell Surface Protein Atlas (CSPA) is a new public resource of experimentally verified cell surface accessible markers and targets for therapeutics.Check out the CSPA website.

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Surfaceome Visualization

PROTTER

PROTTER is an open source tool for the visualization of proteoforms and interactive integration of annotated and predicted sequence features together with experimental proteomic evidence. Check out the PROTTER website.

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Surfaceome Data Analysis

SURFY

The in silico human surfaceome is based on the machine learning algorithm SURFY and represents a new public resource for the visual interrogation of multi-omics datasets for the biomedical community. Check out the SURFY website.

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Check out some of our research highlights:

Team Members

We are hiring.

We are always looking for highly motivated people to join our team!
Get in touch if you are interested.

Bernd Wollscheid

Professor

Emanuela
Milani-Tschudy

Senior Scientist &

Head of Tumor Profiler

Sandra Goetze

Senior Scientist &

SMOC Coordinator &

COO PHRT-CPAC

Audrey van Drogen

Labmanager

Patrick Pedrioli

Senior Scientist &

PHRT Computational Head

Silvana Albert

Tumor Profiler
Data Scientist

Jacqui Hammer

PhD Student

Jonas Albinus

PhD Student

Julia Boshart

PhD Student

Sebastian Steiner

PhD Student

Heidi Funke

PhD Student

Jens Settelmeier

PhD Student

Arend Keller

PhD Student

Martin Gesell

PhD Student

Publications

Check our publication list.

Google Scholar PubMed PaperPile

2018-2022 (selected)

Use of MS-GUIDE for identification of protein biomarkers for risk stratification of patients with prostate cancer.
Sandra Goetze, Peter Schüffler, Alcibiade Athanasiou, Anika Koetemann, Cedric Poyet, Christian Daniel Fankhauser, Peter J. Wild, Ralph Schiess & Bernd Wollscheid.
Clinical Proteomics, 2022

Light-mediated discovery of surfaceome nanoscale organization and inter-cellular receptor interaction networks.
Maik Müller, Fabienne Gräbnitz, Niculò Barandun, Yang Shen, Fabian Wendt, Sebastian N. Steiner, Yannik Severin, Stefan U. Vetterli, Milon Mondal, James R. Prudent, Raphael Hofmann, Marc van Oostrum, Roman C. Sarott, Alexey I. Nesvizhskii, Erick M. Carreira, Jeffrey W. Bode, Berend Snijder, John A. Robinson, Martin J. Loessner, Annette Oxenius, Bernd Wollscheid.
Nature Communications, 2021

Reproducible Determination of High-Density Lipoprotein Proteotypes
Sandra Goetze, Kathrin Frey, Lucia Rohrer, Silvija Radosavljevic, Jan Krützfeldt, Ulf Landmesser, Marco Bueter, Patrick G. A. Pedrioli, Arnold von Eckardstein, Bernd Wollscheid.
Journal of Proteome Research, 2021

CD20 as a gatekeeper of the resting state of human B cells
Kathrin Kläsener, Julia Jellusova, Geoffroy Andrieux, Ulrich Salzer, Chiara Böhler, Sebastian N. Steiner, Jonas B. Albinus, Marco Cavallari, Beatrix Süß, Reinhard E. Voll, Melanie Boerries, Bernd Wollscheid, Michael Reth.
Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2021

The Tumor Profiler Study: integrated, multi-omic, functional tumor profiling for clinical decision support
Anja Irmisch*, Ximena Bonilla*, Stephane Chevrier*, Kjong van Lehmann*, Francisca Singer*, Nora Toussaint*, Cinzia Esposito*, Julien Mena*, Emanuela Milani*, Ruben Casanova*, Daniel Stekhoven*, Rebekka Wegmann*, Bettina Sobottka*, Sandra Götze*, Jack Kuipers*, Jacobo Sarabia del Castillo*,Tumor Profiler Consortium, Rudolf Aebersold+, Niko Beerenwinkel+, Christian Beisel+, Bernd Bodenmiller+, Viktor Kölzer+, Holger Moch+, Lucas Pelkmans+, Berend Snijder+, Markus Tolnay+, Bernd Wollscheid+, Gunnar Rätsch+,=, Mitchell P. Levesque+ (= * Joint first author, + Joint last author, = corresponding authors).
Cancer Cell, 2021

Enzymatic Dissociation Induces Transcriptional and Proteotype Bias in Brain Cell Populations
aniele Mattei, Andranik Ivanov, Marc van Oostrum, Stanislav Pantelyushin, Juliet Richetto, Flavia Mueller, Michal Matheus Beffinger, Linda Schellhammer, Johannes vom Berg, Bernd Wollscheid, Dieter Beule, Rosa Chiara Paolicelli, Urs Meyer.
International Journal of Molecular Sciences, 2020

Standardization and harmonization of distributed multi-center proteotype analysis supporting precision medicine studies.
Yue Xuan, Nicholas W. Bateman, Sebastien Gallien, Sandra Goetze, Yue Zhou, Pedro Navarro, Mo Hu, Niyati Parikh, Brian Hood, Kelly Conrads, Christina Loosse, Reta Birhanu Kitata, Sander R. Piersma, Davide Chiasserini, Hongwen Zhu, Guixue Hou, Muhammad Tahir, Andrew Macklin, Amanda Khoo, Xiuxuan Sun, Ben Crossett, Albert Sickmann, Yu-Ju Chen, Connie R. Jimenez, Hu Zhou, Siqi Liu, Martin R. Larsen, Thomas Kislinger, Zhinan Chen, Benjamin L. Parker, Stuart J. Cordwell, Bernd Wollscheid*, and Thomas P. Conrads*. *shared senior authorship
Nature Communications, 2020

MassIVE.quant: a community resource of quantitative mass spectrometry–based proteomics datasets
Meena Choi, Jeremy Carver, Cristina Chiva, Manuel Tzouros, Ting Huang, Tsung-Heng Tsai, Benjamin Pullman, Oliver M. Bernhardt, Ruth Hüttenhain, Guo Ci Teo, Yasset Perez-Riverol, Jan Muntel, Maik Müller, Sandra Goetze, Maria Pavlou, Erik Verschueren, Bernd Wollscheid, Alexey I. Nesvizhskii, Lukas Reiter, Tom Dunkley, Eduard Sabidó, Nuno Bandeira, Olga Vitek.
Nature Methods, 2020

The hematopoietic stem cell marker VNN2 is associated with chemoresistance in pediatric B-cell precursor ALL
Beat Bornhauser, Anna Rinaldi Gunnar Cario, Thomas Risch, Virginia Rodriguez, Moritz Schuette, Hans- Jörg Warnatz, Nastassja Scheidegger, Paulina Mirkowska, Martina Temperli Claudia Möller, Angela Schumich, Michael Dworzak, Andishe Attarbaschi, Monika Brüggemann, Matthias Ritgen, Ester Mejstrikova Andreas Hofmann, Barbara Buldini, Pamela Scarparo, Guiseppe Basso, Oscar Maglia Giuseppe Gaipa, Tessa-Lara Skroblyn, Truus te Kronnie, Elena Vendramini, Renate Panzer-Grümayer, Blerim Marovca, Malwine Barz, Mathias Hauri-Hohl, Felix Niggli, Cornelia Eckert, Martin Schrappe, Martin Stanulla, Martin Zimmermann, Bernd Wollscheid, Marie-Laure Yaspo, Jean-Pierre Bourquin.
Blood Advances, 2020

Cell-Derived Vesicles as TRPC1 Channel Delivery Systems for the Recovery of Cellular Respiratory and Proliferative Capacities.
Felix Kurth, Yee Kit Tai, Dinesh Parate, Marc van Oostrum, Yannick RF Schmid, Shi Ji Toh, Jasmine Lye Yee Yap, Bernd Wollscheid, Alaa Othman, Petra S Dittrich, Alfredo Franco-Obregón.
Advanced Biosystems, 2020

Surfaceome dynamics during neuronal development and synaptic plasticity reveal system-wide surfaceome reorganization independent of global proteostasis.
van Oostrum M, Campbell B, Müller M, Pedrioli P, Tyagarajan S, Wollscheid B.
Nature Communications, 2020

Classification of mouse B cell types using surfaceome proteotype maps
van Oostrum M, Mueller M, Klein M, Bruderer R, Zhang H, Pedrioli P, Reiter L, Tsapogas P, Rolink A, Wollscheid B
Nature Communications, 2019

Surfaceome nanoscale organization and extracellular interaction networks
Bausch-Fluck D, Milani ES, Wollscheid B.
Current Opinion in Chemical Biology, 2018

The in silico human surfaceome
Bausch-Fluck D, Goldmann U, Müller S, van Oostrum M, Müller M, Schubert OT, Wollscheid B.
Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2018

HATRIC-based identification of receptors for orphan ligands
Sobotzki N, Schafroth MA, Rudnicka A, Koetemann A, Marty F, Goetze S, Yamauchi Y, Carreira EM, Wollscheid B.
Nature Communications, 2018

Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence.
Novy K, Kilcher S, Omasits U, Bleck CKE, Beerli C, Vowinckel J, Martin CK, Syedbasha M, Maiolica A, White I, Mercer J, Wollscheid B.
Nature Microbiology, 2018
FAQ

Questions and Answers.

Still not clear who we are and what we do? Or do you have other questions? Perhaps your questions are answered below, but don't hesitate to contact us if they're not.

Who funds you?

Our research is supported by public funding such as

What else are you involved in?

How can I apply to your lab?

We are always looking for enthusiastic people to join our team. We currently have several vacancies that we are looking to fill. Please apply by e-mailing your CV and an explanation of your motivation to Bernd Wollscheid.

Get in touch with us.

Do you want to be part of exciting discoveries? Let's work together!