How Collaboration Sparked a GPCR Imaging Breakthrough in Chemical Biology
- Dr. GPCR Podcast
- Dec 5, 2025
- 5 min read
Some breakthroughs don’t start with a grant or a roadmap — they start with a question no one expects to matter.
For JB, that moment was a cold email from a biologist he’d never met, asking if he could synthesize a molecule “when you’re back in Munich.” That simple ask pulled a young chemist out of the fume hood and into the messy, electrifying world of live-cell biology.
What followed — a trip to London, confocal imaging marathons, and a partnership built on trust and curiosity — reshaped both careers and helped unlock a new generation of GPCR imaging tools. This is the story of how collaboration quietly rewires a field.
This collaboration would become the foundation of a GPCR imaging breakthrough that neither of them anticipated.
How a Collaboration Led to a GPCR Imaging Breakthrough
JB didn’t set out to contribute to a GPCR imaging breakthrough, but a simple molecule request set the entire trajectory in motion.
He was a PhD student studying ion channels — living in a world defined by reaction mechanisms, synthetic routes, and the reassuring logic of chemistry. Then the unexpected request arrived.
David Hodson needed molecules that were only one synthetic step beyond what JB was already making. The ask was simple; the impact wasn’t. That brief exchange connected two people who had never met but were equally driven by curiosity.
When David later shared early data — including a moment where he realized he could image an entire islet — it became clear that this wasn’t just a small contribution. It was the start of a scientific partnership with the potential to shift how GPCRs could be visualized in their native environments.
How Chemistry and Islet Biology Converged to Enable a GPCR Imaging Breakthrough
The collaboration deepened when JB traveled to London, a trip that unexpectedly accelerated what would become a GPCR imaging breakthrough.
What he expected to be a technical visit became a complete reframing of how he thought about biological systems.
Instead of round-bottom flasks, he was looking at living cells under a confocal microscope. Freshly isolated pancreatic islets. Real-time calcium activity. Signaling waves pulsing across clusters of beta cells.
Seeing those images, he realized just how different biological reality is from chemical idealization. Molecules weren’t abstract entities anymore — they were tools that could illuminate dynamic, excitable tissues and reveal mechanisms driving hormone secretion.That shift in perspective became foundational.
It would later shape how he designed fluorescent probes, how he evaluated biological constraints, and how he approached GPCR imaging as both a chemical problem and a physiological one.
How Chemical Probes Transformed GPCR Imaging and Outperformed Antibodies
As JB continued exploring the biology, a major obstacle emerged: validated antibodies for GPCRs, including GLP-1R, were inconsistent and incompatible with high-resolution imaging. For a field that depends on understanding where receptors actually are — and how many are available at the cell surface — this was a major limitation.
The shift toward chemical probes became a defining moment in achieving a true GPCR imaging breakthrough.
Chemical probes offered a solution. They could be engineered to target surface-exposed receptors, remain stable across batches, support live-cell imaging, and tolerate super-resolution workflows. There was one challenge: JB had never synthesized peptides. The project required designing peptide–fluorophore conjugates that would bind GLP-1R with high specificity. Instead of stopping, he teamed up with a peptide specialist at the Max Planck Institute.
Together, they built the first generation of GLP-1R fluorescent ligands — probes precise enough to visualize the receptor across islets, tissue slices, and ultimately living animals.
Early images showed clean, bright labeling across whole pancreatic islets. That breakthrough launched the first wave of GLP-1R visualization studies and opened the door to deeper questions about receptor distribution, density, and trafficking.
Designing Reliable GPCR Imaging Tools for Real Biological Systems
Success brought new challenges. Chemical probes may be elegant, but biology isn’t. Tissue is messy.
Cells behave differently day to day. Receptors internalize, traffic, recycle, and degrade.
To build tools that performed consistently, JB and collaborators shifted toward a more rigorous parallelized screening approach.
Instead of testing one compound at a time, they evaluated multiple probes in the same experimental conditions — same transfection, same cells, same humidity, same everything.
This strategy accelerated discovery and reduced noise, helping them understand how each design change influenced labeling, specificity, and photophysical behavior. It also gave them confidence in how the probes would perform once shipped to external labs.
The payoff was substantial. These optimizations enabled dual-color labeling strategies, surface-selective imaging, and ultimately in vivo visualization.
These parallelized experiments were critical for turning early ideas into a reproducible GPCR imaging breakthrough.
Two-photon microscopy experiments showed GLP-1R signaling in intact animals — a milestone that demonstrated just how powerful well-engineered chemical tools can be when paired with the right biology.
Collaboration as the Driver Behind Today’s GPCR Imaging Breakthroughs
Behind the technical success lies a partnership shaped by trust, shared energy, and a willingness to learn each other’s language.
JB brought chemical intuition and a love for toolmaking. David brought deep experience in islet biology, calcium imaging, and tissue physiology.
Over the years, they learned from each other in ways that shifted both careers. JB gained a grounded understanding of tissue heterogeneity, signal variability, and the biology that makes GPCR research challenging. David picked up unexpected chemistry insights — including a well-loved lesson involving acetonitrile in conjugation reactions.
What made the collaboration durable wasn’t simply aligned expertise. It was a shared sense of fun, the kind of scientific joy that makes late-night imaging sessions feel lighter and big failures feel solvable. That chemistry — human chemistry — is what allowed the science to move as quickly as it did.
Curiosity also played a central role.
JB emphasizes how much of their progress came from staying open, asking questions freely, and engaging people at conferences regardless of title or reputation. Many of the connections that shaped the probes’ development came from simple conversations that began with genuine scientific interest.
Their trust-driven collaboration is ultimately what allowed the GPCR imaging breakthrough to take shape.
The Future of GPCR Imaging Breakthroughs: AI, Multiplex Tools, and In Vivo Discovery
Today, JB leads an interdisciplinary group at the FMP in Berlin — chemists, theorists, biochemists, toxicologists, and cell biologists — all working toward the same goal: building better tools for visualizing cell-surface proteins, especially GPCRs.
The work now stretches far beyond a single receptor. His team is exploring AI-enabled probe design, multiplex fluorescent strategies that allow visualization of multiple GPCRs at once, and approaches capable of mapping receptor crosstalk at nanometer scale.
They’re also performing increasingly complex imaging experiments that capture receptor dynamics in intact tissue and live animals, expanding what’s possible in both basic research and translational settings.
What started as one molecule request is now a platform vision — a future where any GPCR could be illuminated with high precision, in any tissue, across multiple colors, with tools designed as much by computation as by human intuition.
And it all began with a simple moment of collaboration.
This conversation is part of a three episode series produced in collaboration with our partners at Celtarys Research.
If this behind-the-scenes story resonated, you’ll love the full conversation.
🎧 Listen to the full episode
If JB's story resonates
Comments