Jean-Philippe Pin: glutamate filling his head

In a few months, Jean-Philippe Pin will celebrate his 40th anniversary atthe Institute of Functional Genomics (IGF) in Montpellier. "Forty years working on glutamate receptors," jokes the CNRS research director. Listening tohimtalk about his work, his loyalty to his subject becomes clear. Testing the role of this major neurotransmitter reveals the complexity of brain regulation, with therapeutic avenues for the treatment of nervous system disorders such as schizophrenia and neurodegenerative diseases. And let's say it right away, Jean-Philippe Pin no longer needs to prove himself. He received the prestigious Lamonica Prize in neurology in 2022, eleven years after receiving the CNRS Silver Medal.

When asked about his career, Jean-Philippe Pin does not begin with his awards but with his early days. As a master's student, he joined Joël Bockaert's laboratory at the Center for Pharmacology and Endocrinology in Montpellier, which later becamethe IGF. The young researcher immersed himself in studying the mechanism of action of glutamate, whose major role as a neurotransmitter was then unknown. "The scientific community did not imagine at the time that this simple amino acid could be the most important neurotransmitter, since its receptors are found in 80% of synapses," he explains. After participating in the discovery of G protein-coupled glutamate receptors in 1985—summarized by the laborious acronym mGluR—the scientist joined the CNRS in 1988. He then headed to the United States for postdoctoral research at the Salk Institute in California, about which he laconically remarks, "I watch the trains go by. "In other words, he participated in the race to sequence the genes of mGluR receptors, but other teams discovered the eight genes that code for the eight known receptors before he did.

The Arpege technology platform

A good loser, Jean-Philippe Pin then turned his attention to deciphering their activation mechanisms. His goal was to discover new avenues for treating neurological and psychiatric diseases. These receptors have proven to be interesting drug targets. In the molecular pharmacology department he created in 2003 at the IGF, Jean-Philippe Pin developed new high-throughput analysis techniques dedicated to the study of this category of receptors. Easy to say, but the financial resources still had to be found. Collaborations with pharmaceutical companies opened up new avenues, but these came to nothing after a few years due to a lack of convincing clinical results.

Ultimately, salvation will come from other collaborations. Jean-Philippe Pin has created the Arpege technology platform, which is open to researchers who want to test G protein-coupled receptors. " This pooling of resources gives us access to engineers and equipment comparable to those in industry," says the researcher. The partnership with the biotechnology company Cis-Bio, which supplies laboratories with screening kits, also gives his team access to technologies and tools "unavailable to our academic competitors." To complete the scientific and technological triptych, a Chinese postdoctoral fellow enabled the IGF to set up a collaboration with a laboratory in Wuhan in 2004."All the research on atomic structure is done there, using equipment that is inaccessible to our teams here, such as electron microscopes,"says the researcher, who holds weekly video meetings with his colleagues in the Chinese city that has become known as the birthplace of COVID-19.

The medicine of the future

But research is not just a question of resources, of course. Among his scientific insights, a new hypothesis about glutamate receptors has proven to be correct: the receptors are made up of two parts that are not necessarily identical. This previously unknown heterogeneity is now "recognized by the scientific community," says the man who says he likes to "challenge dogmas in science." His other current challenge is to focus on antibodies rather than chemical molecules as a treatment. With his team, he is testing the action of antibodies on the famous mGluRs in the brain and their effects on schizophrenia.

This time, he is one step ahead, imagining the medicine of the future by working on treatments based on photo-controllable molecules. The advantage? Triggering the activity of a molecule using a diode, which allows its action to be precisely localized. "It's really important to be able to target a specific area of the brain because the same molecule can have different effects depending on whether it acts in the cerebellum or the globus pallidus, for example,"explains Jean-Philippe Pin. This year's Lamonica Prize recognizes these prospects for new therapeutic agents and awards €100,000 to the IGF and €10,000 to its director between 2011 and 2020.