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Interview | Health & life sciences

Hugues Nury - Understanding the functioning of a family of neuronal receptors (Pentabrain)

The structural study of membrane proteins helps scientists understand how the nervous system works at the molecular level. Hugues Nury’s project, entitled "PentaBrain" was selected in 2014 by the ERC. It aims to understand the functioning of a family of neuronal receptors through the study of their structure.
Hugues Nury likes to say that he works in the field of structural neuroscience. “While neuroscience investigates the nervous system from a biological and/or psychological standpoint, I am interested in the structure of its protein—that of membrane protein in particular,” he says.

Membrane proteins, otherwise known as neuroreceptors, are located on the surface of neurons, and receive information from other neurons via neurotransmitters. The neuroreceptors open up and allows ions through, thus enabling the transmission of an electrical signal in the neurons. “Neuroreceptors play an essential role in the learning process, and also in pharmacology, since virtually all psychoactive drugs have an effect on them,” Nury says. Yet their study proves quite complex, since like other membrane proteins, neuroreceptors are difficult to handle and to grow in labs.

Now this scientist focuses his efforts on a specific receptor of a neurotransmitter called serotonin. This receptor is the target of numerous anti-nausea drugs used to treat the side effects of chemotherapy. Providing a description of its structure takes as much as several years of work. It requires growing, extracting, and purifying the neuroreceptor and, finally, managing to crystallize it. This last step, essential to visualize its structure, proved particularly complex. “We couldn’t obtain a crystal that was organized enough to allow for a relevant diffraction figure... We eventually had to use llama antibodies to stabilize the protein!” It became a success in 2014. Now Nury’s team is continuing its research to understand protein dynamics using methods such as the coupling of crystallography and electron microscopy.

Hugues Nury (Institute of Structural Biology - CEA / CNRS / Université Grenoble Alpes, Grenoble) aims to understand the functioning of a family of neuronal receptors, in a project selected by the European Research Council in 2014 getting € 1.5 million over five years.



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IBS
Center : Grenoble
Expertise : Nervous systems