Jean-Philippe Pin: His Head Is Full of Glutamate

In a few months, Jean-Philippe Pin will celebrate his 40th anniversary atthe Institute of Functional Genomics (IGF) in Montpellier.“I’ve been working on glutamate receptors for 40 years,” says the CNRS research director with a smile. As he talks about his work, his dedication to his field of study becomes clear. Investigating the role of this major neurotransmitter sheds light on the complexity of regulatory mechanisms in the brain, opening up therapeutic avenues for treating nervous system disorders such as schizophrenia and neurodegenerative diseases. And let’s just 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 being awarded the CNRS Silver Medal.

When asked about his career, Jean-Philippe Pin doesn’t start 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 little understood at the time.“The scientific community had no idea back then that this simple amino acid could be the most important neurotransmitter, since its receptors are found in 80% of synapses,” he explains. After contributing to the 1985 discovery of G-protein-coupled glutamate receptors—summarized by the cumbersome acronym mGluR—the scientist joined the CNRS in 1988. He then headed to the United States for a postdoc at the Salk Institute in California, about which he remarks laconically, “I watch the trains go by.”In other words, he was part of the race to sequence the genes for the mGluR receptors, but other teams discovered the eight genes encoding the eight known receptors before he did.

The Arpege Technology Platform

A good sport, Jean-Philippe Pin then turned his attention to unraveling their activation mechanisms, with the goal of discovering novel therapeutic approaches for treating neurological and psychiatric disorders. Indeed, these receptors have proven to be promising drug targets. In the Department of Molecular Pharmacology, which he founded in 2003 at the IGF, Jean-Philippe Pin developed new high-throughput analytical techniques dedicated to studying this class of receptors. That’s easier said than done, however, as funding still had to be secured. Collaborations with pharmaceutical companies opened up avenues, but they came to an end after a few years due to a lack of conclusive clinical results.

Ultimately, the solution will come from other collaborations. Jean-Philippe Pin has created the Arpege technology platform, open to researchers who wish to test G protein-coupled receptors. “This collaboration gives us access to engineers and equipment comparable to those in the industry,” the researcher notes with satisfaction. 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 this scientific and technological trio, a Chinese postdoctoral fellow enabled the IGF to establish a collaboration as early as 2004 with a laboratory in… Wuhan.“All the research on atomic structure is conducted there thanks to equipment unavailable to our teams here, such as electron microscopes,”emphasizes the researcher, who holds weekly video conferences with his colleagues in the Chinese city that has become known as the birthplace of COVID-19.

The Medicine of the Future

But research, of course, isn’t just a matter of resources. Among his sound scientific intuitions, a new hypothesis about glutamate receptors has proven correct: the receptors are made up of two parts that aren’t necessarily identical. This previously unknown heterogeneity is now“recognized by the scientific community,” says the researcher, who claims to enjoy“challenging scientific dogma.” His other current challenge is to focus on antibodies rather than chemical molecules as a treatment. Together with his team, he is testing the action of antibodies on the well-known mGluRs in the brain and their effects on schizophrenia.

Once again one step ahead of the curve, he is envisioning the medicine of the future by working on treatments based on light-controlled molecules. The benefit? Triggering a molecule’s activity using a diode, which allows its action to be precisely targeted.“It’s crucial 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, awarding 100,000 euros to the IGF and 10,000 euros to the individual who served as its director from 2011 to 2020.