Beatriz Blanco-Redondo: Adhesion GPCR Discovery in Drosophila

Adhesion GPCRs are among the least characterized receptor families in the human genome - and in Drosophila melanogaster, three of the five known adhesion GPCRs had no documented function, expression pattern, or signaling profile when Beatriz Blanco-Redondo's group began working on them. The receptors were named after condiments - ketchup, mayo, and remulate - not out of irreverence, but because no functional data yet existed to guide any other kind of nomenclature.

Blanco-Redondo, group leader at the University of Leipzig, uses CRISPR engineering, epitope tagging, and in vivo behavioral assays to build the first systematic characterization of these receptors from the ground up. Her primary focus is remulate - a neuronal adhesion GPCR with a human ortholog linked to vascular malformations and blood-brain barrier dysfunction in vertebrate models. The fly system makes it tractable: new lines in weeks, knockouts in months, and behavioral readouts that connect receptor loss to nocifensive phenotypes in larvae.

For Blanco-Redondo, the pull toward this work is not abstract. Remulate is the receptor she secured funding to study, the one her first PhD student built an entire project around, and the one that still does not have a complete localization map. This conversation covers what it looks like to do receptor biology when you are writing the first chapter - with no antibodies, no prior literature, and no established toolkit to fall back on.

About the Guest

Beatriz Blanco-Redondo is a group leader in the Department of Biochemistry at the University of Leipzig, where she studies adhesion GPCRs in Drosophila melanogaster. Her research focuses on characterizing the localization, signaling, and in vivo function of previously unknown adhesion receptors in the fly nervous system and gut. She trained in protein biochemistry and neuroscience, completing her PhD in Germany and her postdoctoral work at Columbia University, where she worked on ALS models using mouse systems. Since returning to Europe, her research has centered on receptor biology at the intersection of basic discovery and translational relevance.

Scientific Themes of the Conversation

1. First-contact receptor characterization - what it means to study a GPCR with no prior functional data
   

2. Genetic tools for adhesion GPCR research in Drosophila - CRISPR, epitope tagging, and knockout strategies
   

3. The logic of model organism selection - speed, genetic tractability, and translational value
   

4. Nocifensive behavior as a readout for neuronal receptor function in larvae
   

5. Human ortholog connections - from fly adhesion GPCRs to vertebrate vascular and neurological disease
   

6. Career decisions in academic science - uncertainty, reentry, and the conditions that keep scientists in the lab

Key Insights from the Conversation

1. Three adhesion GPCRs in Drosophila were functionally unknown until recently

When Blanco-Redondo's group began this work, five adhesion GPCRs were known in the fly - but only two had any functional characterization. The other three had no documented expression pattern, signaling data, or phenotype. The approach was systematic: generate knockouts, introduce epitope tags, observe what breaks, and build the picture from scratch. There was no shortcut available because there was no prior literature to build on.

2. Naming receptors after condiments signals where the field actually stands

Ketchup, mayo, and remulate were named in the absence of functional data that would normally guide nomenclature. It is a small detail, but it marks something real about the state of adhesion GPCR biology in insects: these receptors exist in a space where the biology precedes the vocabulary. The playfulness of the naming reflects the honesty of the situation.

3. Remulate connects fly neuroscience to human vascular and neurological pathology

In the peripheral nervous system of Drosophila larvae, loss of remulate disrupts nocifensive behavior - the animal's response to aversive stimuli. The human ortholog has been associated with vascular malformations and blood-brain barrier dysfunction in vertebrate models. That thread, from a behavioral assay in a fly larva to a clinical phenotype in mice, is what gives the model system its translational justification.

4. Antibody limitations drive the methodological design

Because the antibody landscape for adhesion GPCRs is sparse - and largely underdeveloped for fly receptors - Blanco-Redondo's group relies on CRISPR-introduced epitope tags to track receptor localization in vivo. This is not a workaround. It is a deliberate strategy that delivers spatial resolution that antibody-based approaches cannot offer for these targets at this stage of the field.

5. Drosophila generations close the experimental feedback loop

A new fly line is ready in one to two weeks. A knockout can be generated and validated in two to three months. For receptor biology that requires iterative genetic manipulation - knocking out, tagging, rescuing, observing - this compression of experimental time changes which questions are tractable within a single grant period. It is not incidental to the science; it is part of the scientific logic.

6. Reconsidering a career is not the same as leaving science

Blanco-Redondo describes a period after returning from New York when she was genuinely uncertain about continuing in the lab. The decision to stay came from a specific opportunity, a specific mentor, and a specific set of questions she hadn't yet answered. It did not resolve into a clean narrative. It was uncertain, and she says so plainly.

7. Negative results need infrastructure, not just tolerance

Blanco-Redondo and Yamina discuss the cost of unpublished negative data - particularly for PhD students working within three-year funding windows. The argument is not sentimental. If a failed approach were citable, it would shorten the path for the next researcher attempting the same thing. Some journals are beginning to accept negative data, and both agree this matters structurally.

Episode Timeline

Timestamps are AI-generated from the transcript and may not reflect the final edited episode precisely. Verify against the published video before use.

• 00:00 - Sponsor intro: GeneTex and Eurofins DiscoverX

• 00:29 - Introduction of Beatriz Blanco-Redondo; icebreaker

• 01:15 - Career path: from Spain to Germany, and the decision to go further

• 05:57 - Dr. GPCR University mid-roll

• 06:17 - Life in New York; comparing research cultures across continents

• 08:30 - How adhesion GPCRs entered the picture, and the shift toward receptor biology

• 11:49 - Research program in Leipzig: three unknown adhesion GPCRs in Drosophila

• 13:57 - Naming remulate, ketchup, and mayo; why remulate became the primary focus

• 15:47 - Lab methods: CRISPR, epitope tagging, colony generation timelines

• 17:29 - Behavioral and phenotypic readouts; nocifensive responses in larvae

• 18:48 - The human ortholog of remulate and connections to vascular and neurological disease

• 22:58 - What first-contact receptor characterization actually looks like

• 26:02 - Career turning points; uncertainty on returning from the US

• 33:25 - Advice for scientists working on adhesion GPCRs and difficult model systems

• 35:26 - The case for publishing negative results; pressure on PhD timelines

• 40:54 - Upcoming GPCR conferences in Leipzig and Dusseldorf

Selected Quotes