Jane Lamerdin and Gaurav Agrawal: Building GPCR Assays That Reflect Real Biology

GPCRs spent years in the background while pharmacology chased other targets. Obesity and GLP-1 biology changed that, and the largest target class is once again at the front of drug discovery.

In this conversation, two Eurofins DiscoverX scientists reflect on what nearly three decades of building GPCR assays has taught them about what a trustworthy assay actually requires.

The recurring theme is physiological relevance. Overexpressing a receptor produces a big, convenient signal, but it distorts the pharmacology and drifts away from what happens in a real cell. Lamerdin and Agrawal explain why the field, and increasingly regulators, now expect assays built closer to native expression, and why that raises the technical bar considerably. Along the way they discuss the receptors that simply refuse to yield an assay, from adhesion GPCRs to orphans trapped in the endoplasmic reticulum, and the long road from a discovery-grade assay to one robust enough for potency and lot release.

For Agrawal it is personal: he spent his PhD on four GPCRs and now stewards 289, carrying those early lessons into every assay his team validates.

About the Guests

Jane Lamerdin is VP of R&D at Eurofins DiscoverX, where she oversees development of novel cell-based assays and tools for both portfolio expansion and client-focused projects. She brings more than twenty years of industry experience across diverse cell-based assays, supporting client drug discovery campaigns, method development, and qualification of assays for late-stage biologics. Her background spans high-throughput, molecular, and systems biology research, which lets her speak to what an assay needs at every stage of a program.

Gaurav Agrawal earned his PhD in cell and molecular biology from the Indian Institute of Science, studying how GPCRs activate. During his postdoc at UC San Diego, he discovered a novel intracellular trafficking pathway essential for organelle biogenesis. At Eurofins DiscoverX, Agrawal leads market development for the cell-based assay portfolio and supports method transfers to CROs and CDMOs for biologics and biosimilars, keeping him in close contact with the scientists running these assays day to day.

Scientific Themes of the Conversation

• Physiological relevance versus overexpression as the standard for a credible cell-based assay

• The company's arc from cyclic AMP screening into arrestin and internalization biology

• The obesity and GLP-1 resurgence that returned GPCRs to the front of drug discovery

• De-orphanizing GPCRs, including receptors stuck in the endoplasmic reticulum

• Moving a single GPCR assay from discovery through potency testing and lot release

• Community and client feedback as the real engine of new product development

Key Insights from the Conversation

Overexpression buys signal at the cost of truth. A single receptor can trigger a large, amplified cyclic AMP response, which makes overexpression assays convenient but unrepresentative. The easy readout drifts away from the biology researchers actually want to measure.

Physiological relevance is now an expectation, not a preference. Regulators have begun telling companies directly that assays need to reflect near-primary expression levels. That raises the technical bar, since detecting such low expression pushes the limits of available methods.

One assay is not one assay. A cell line that is excellent for discovery screening can be unsuitable for potency and lot release, where plate-to-plate, analyst-to-analyst, and year-to-year consistency become non-negotiable. Bridging that gap takes months of hardening work.

Failure is documented, not buried. Decades of careful record-keeping on assays that never worked, from adhesion GPCRs to certain photoreceptor-like targets, let the team avoid reinventing dead ends and focus energy where progress is still possible.

GPCRs never left; the attention did. For years the field's spotlight drifted to checkpoints and T-cell receptors. The obesity and type 2 diabetes wave brought GPCRs back to the front seat, and with it a fresh round of questions about how these receptors actually work.

Scientists first, vendor second. The guests frame their work as talking to peers who understand the same pains, not selling a catalog. The support inbox and community collaborations feed directly back into what gets built next.

Episode Timeline

Timestamps were generated using AI for readability.

• 00:00 Meet the Eurofins DiscoverX scientists

• 03:20 From four receptors to 289: Agrawal's path into GPCRs

• 07:00 The Human Genome Project to pharmacology: Lamerdin's route

• 10:40 Why the largest target class still surprises them

• 21:40 How DiscoverX began, from cyclic AMP to arrestin

• 33:20 The assays that refused to work

• 36:30 De-orphanizing GPCRs stuck in the ER

• 46:40 Obesity, GLP-1, and the return of GPCRs

• 47:40 Physiological relevance as the real bottleneck

• 53:40 One message: scientists first

Selected Quotes