Welcome to the Wollscheid Laboratory at ETH Zürich
Every cell talks to the world through its surface. We build the tools to listen in, and turn what we hear into the next generation of medicines.
The big idea
The surfaceome is the gatekeeper between a cell's inner life and the world outside, a crowded landscape where proteins gather into neighbourhoods to sense, decide and signal.
Signals pass from the extracellular world, through the surfaceome, into the cell's interior, one connected network. Learn to read it at molecular resolution, and you can understand, and one day rewrite, how cells communicate in health and disease.
What we study
The surfaceome is the complete set of proteins on the outer surface of a cell's plasma membrane, the interface where medicine acts. It is the docking site for hormones, the entry point for viruses, the surface the immune system reads, and the target of most of today's biologic drugs.
These proteins don't act alone. They cluster into functional communities, and by mapping which proteins sit next to which we reveal not just single targets but co-target pairs, combinations far more selective for a diseased cell than any protein on its own.
A sense of scale
If one surface molecule were blown up to the size of a person, the surface of a single immune cell would cover roughly three times the area of New York's Central Park. Proteins, like people, gather in neighbourhoods to get things done, each "baseball diamond" is a place where a specific job happens. Step off the field, and the game stops.
We read the nanoscale architecture of the surfaceome and translate it into next-generation diagnostics and therapeutics for patients.
Central Park, New York, an aerial analogy for the cell surface
Prefer to listen? A general-audience podcast about the lab's research, what the surfaceome is, and why mapping the cell surface matters.
Listen to the podcast →The toolkit
Fewer than thirty proteins underpin every antibody therapy in use today. To go beyond them, you need to see the surface as it really is, crowded, dynamic and organised into communities.
Over two decades we've built a toolkit that spans chemistry, biology, machine learning and mass spectrometry: to capture the surfaceome, predict it, and watch it organise on living cells in real time.
Cell Surface Capture (CSC) is the founding method of the field, antibody-free chemical labelling that selectively enriches N-glycosylated proteins exposed on living cells, revealing both the identity and the relative quantity of the receptors a cell displays. These measurements feed the Cell Surface Protein Atlas (CSPA), the community's reference surfaceome spanning dozens of human and mouse cell types. Because it reads the surface directly on intact cells and needs no prior knowledge of the targets, CSC captures the receptor landscape exactly as the cell presents it, an unbiased starting point for finding disease-selective receptors.Nat. Biotechnol. 2009
LUX-MS is our optoproteomic technology: pulses of light and singlet-oxygen chemistry capture split-second protein contacts on and between living cells. It resolves the nanoscale organisation of receptors, charting the surface protein communities and neighbourhoods that make a target selective for a diseased cell, and reveals which cells physically talk to each other, all without genetic engineering. Because the labelling is triggered by light, experiments can be timed and localised with precision, showing how receptor neighbourhoods rearrange as cells interact and change state.Nat. Commun. 2021
Ligand-Receptor Capture (LRC) chemistry pinpoints exactly which receptors a drug, antibody, ligand or pathogen engages on living cells. TriCEPS couples the ligand of interest and covalently crosslinks it to its receptor's glycan; the water-soluble HATRIC variant extends the approach to de-orphanise interactions, turning proximity into a directly identifiable, druggable target. Because it works on native cells and tissues rather than purified proteins, an interaction found in the dish can be traced back to the receptor that actually drives the biology in disease.Nat. Biotechnol. 2012Nat. Commun. 2018
SURFY is a machine-learning predictor of the human surfaceome. Trained on high-confidence experimental evidence, it defines ~2,886 proteins likely to reach the cell surface, and explains why. It scores every human gene product for surface localisation and pairs each prediction with the evidence behind it, turning a sprawling proteome into a ranked, searchable shortlist. That makes SURFY a fast first filter, an in-silico reference map that narrows thousands of candidates to the few worth testing before ever touching a cell.PNAS 2018
Protter renders any protein's sequence and membrane topology as an interactive map, layering annotated features and experimental proteomic evidence directly onto the drawing, so a surfaceome dataset becomes a publication-quality illustration you can read at a glance. Users can overlay their own data, glycosylation sites, transmembrane domains, peptides identified by mass spectrometry, and export figures ready for publication. Freely available online, it has become one of the field's most widely used tools for visualizing cell surface receptor proteoforms.Bioinformatics 2014
High-throughput, data-independent mass spectrometry turns millions of spectra into quantitative proteotype maps, the digital proteome of a cell. This data layer lets us compare surfaces across cells, patients and disease states, and validate candidate targets at scale. The same hybrid-PRM/DIA approach reads out phosphorylation-modulated signalling networks, quantifying targeted phospho-sites and discovery-wide changes in one run, so the cell's active signalling state can be captured alongside its proteome.Clin. Proteomics 2024
Open science
Discovery depends on sharing. We publish our surfaceome resources openly, atlases, predictors and visualisers used by thousands of researchers worldwide.
Each tool takes years of measurement and turns it into something anyone can query in seconds: a searchable map of the cell surface, a prediction for any human protein, an interactive view of the evidence.
Experimentally verified, cell-surface-accessible proteins and therapeutic targets across dozens of human and mouse cell types, the community's reference surfaceome. Built from Cell Surface Capture data, it lets anyone look up which receptors a given cell actually displays, compare surfaces between cell types, and spot the markers that set a diseased cell apart. What once took a dedicated proteomics campaign is now a few clicks, a trusted starting point for target discovery in labs around the world.
Open CSPA → PredictorA machine-learning predictor and browser for the 2,886-protein human in-silico surfaceome, ask whether any human protein is likely to reach the surface, and why. Every call comes with the features and confidence behind it, so you can weigh a candidate at a glance instead of trusting a black box. It turns "is this protein a possible surface target?" from days of literature digging into an instant, evidence-backed answer, before you commit a single experiment.
Open SURFY → VisualisationAn open-source tool for drawing proteoforms and layering annotated and experimental evidence directly onto a protein's sequence and membrane topology. Drop in your own peptides, glycosylation sites or modifications and Protter renders a clear, publication-ready topology diagram in seconds. It has become a lab staple for communicating membrane-protein biology, one figure that shows, at a glance, exactly where the evidence sits on the protein.
Open Protter →From map to medicine
By reading the cancer surface at scale, and the communities proteins form there, we surface the novel, cancer-selective targets and co-target pairs that next-generation medicines have been waiting for.
Decode the surfaceome of a diseased cell at molecular resolution, every accessible protein, and the neighbourhoods they cluster into. Cell Surface Capture, LUX-MS and proteotyping turn the living surface into data.
Read which proteins sit side by side to reveal novel, cancer-selective targets, and co-target pairs whose combination marks a diseased cell far more precisely than any single protein others have mined.
Convert validated targets and target pairs into precision biologics, antibody-drug conjugates, bispecifics and T-cell engagers, designed to hit the diseased cell and spare the healthy one.
Advance first-in-class, surfaceome-directed therapies toward the patients with the greatest need, the discovery-to-clinic path now proven by the lab's spin-off, DISCO Pharmaceuticals.
Spin-off · Schlieren · Cologne · Boston
Built on the discovery platform pioneered in this lab, DISCO combines cell-surface proteomics with advanced protein-community mapping to reveal previously inaccessible targets and target pairs, and to build first-in-class, surfaceome-directed medicines: bispecific antibody-drug conjugates and T-cell engagers. Because DISCO reads the surfaceome as a connected system rather than one protein at a time, it can pinpoint target pairs that flag a diseased cell while sparing healthy tissue, exactly the selectivity next-generation therapies depend on. That map-first approach is what turns a molecular atlas into a pipeline: every target is discovered, validated and prioritised on the same platform. With its technology now proven through major pharma partnerships and a growing wave of surfaceome-directed candidates, DISCO is staking out the cell surface as one of the richest, and least-exploited, frontiers in modern drug discovery.
Second spin-off · Schlieren
Dualsystems Biotech puts the lab's ligand-receptor capture technology, LRC-TriCEPS and HATRIC-LRC, licensed from ETH Zürich, directly into the hands of scientists in academia and industry worldwide. Through ready-to-use kits and contract services, any team can pinpoint the receptors and off-targets of a ligand, drug, antibody or virus on living cells, in their native state and without genetic modification, answering the deceptively simple question that so often stalls drug discovery: what does my molecule actually bind? From de-orphanising a receptor to flagging a therapeutic's off-target liabilities long before it reaches the clinic, it turns what was once a bespoke, months-long experiment into a routine, reproducible readout. It is how a discovery made at the bench becomes an everyday tool for the global research community. Watch the TriCEPS movie to see how it works.
Visit Dualsystems →The next frontier
Featured project · in collaboration with Roche
The next frontier is intercellular communication, how one cell's surface engages another's. Nowhere is this more consequential than the immunological synapse, the contact zone where a T cell decides whether to kill.
PhD researcher Arend Keller, together with the Roche Innovation Center, is using light-based proximity labeling (SILAC LUX-MS) to map the “artificial” synapse that a T-cell-bispecific antibody, glofitamab (CD20×CD3), builds between a patient's T cell and a lymphoma (DLBCL) cell. Reading that interface at molecular resolution turns a black box into a blueprint for better therapies.