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Juan Reguera, a long-term ESRF user specialised in emerging diseases, wins prestigious award

28-10-2024

Long-term ESRF user Juan Reguera, Director of Research at Inserm and head of the ‘Viral Macromolecular Complexes’ team (CNRS – Aix-Marseille Université), has just been awarded the 2024 Lucien Tartois Prize by the Fondation de la Recherche Médicale for his outstanding career. Reguera’s research focuses on the mechanisms of infection by emerging zoonotic viruses, particularly those that can jump from animals to humans.

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The prize recognizes Reguera’s groundbreaking contribution in understanding the stages of viral infection in order to combat emerging viral threats. 

In particular, Reguera’s research has revealed key mechanisms that viruses use to replicate themselves, notably in Bunyavirus, which causes Rift Valley fever, and the Chikungunya virus. Insights into the molecular structure of the enzymes and complexes involved in viral reproduction are critical for the development of future vaccines and antiviral drugs.

Juan Reguera started coming to the ESRF back in 2007. He highlights the ESRF’s impact on his work: “The ESRF has, all along my career, been central in the structural determination of proteins and macrocomplexes. It has been a critical part of all my scientific research”, he says.

Focus on Chikungunya

The Chikungunya virus, transmitted by mosquitoes, causes infections that are characterised by fever, rashes, and debilitating joint pain. Although infections are rarely lethal, in some cases symptoms can persist for years. Chikungunya fever is endemic in Africa, Southeast Asia, the Indian subcontinent, Pacific Region and in the (sub) tropical regions of the Americas.

Reguera’s team has been investigating this virus for several years using the Cryo-Electron microscope (CM01) at the ESRF. In a recent publication in Nature Communications, Reguera and his team uncovered how the nsP3 protein of the Chikungunya virus plays a crucial role in infection by forming tubular structures within cells. These tubes help the virus to replicate and spread.

This research builds on prior work, including studies published in PNAS and Nature, where Reguera’s team also used the CM01 facility to reveal the structure of the nsP1 protein. They found nsP1 forms pores and interacts with molecules essential for capping viral RNA, a key mechanism that allows the virus to evade the host’s immune defenses.

Taken together, these findings offer critical structural insights that are key to understand how viruses hijack the host cells and evade the immune system, which could lead to new ways to block the virus and hence potential avenues for antiviral treatments.

What is next? Reguera explains: “Our main goal right now is to be able to reconstitute the viral replication complexes to characterise their mechanisms of RNA synthesis. This will be instrumental to find inhibitors to block viral replication and develop effective antivirals for the treatment of Chikungunya fever disease”.

Strengthening biomedical research

“We are very proud that Reguera’s research, with so much potential impact in the livelihood of people all over the world, has been recognised with this award”, says Michael Krisch, ESRF Director of Research for Life Sciences.

The ESRF is currently strengthening its scientific capabilities in health-related research, particularly with the Cryo-Electron microscope, the Structural Biology beamlines, the new BM18 tomography beamline, which leads the Human Organ Atlas project, and the planned Nano-Imaging beamline for life sciences. “Our aim is to equip the community with a comprehensive suite of tools to drive groundbreaking research”, concludes Krisch.

In this context, the recognition of Reguera’s work highlights the importance of understanding virus-host interactions in combating emerging infectious diseases, an area where ESRF plays an increasingly supportive role with its cutting-edge facilities.

Juan Reguera is now working on projects about the use of the Cryo-Electron microscope: "In the future we would like to run cryo-electron tomography workflows at the ESRF, in order to be able to look how the replication complex behaves at different stages of infection inside cells. This represents an exciting new outlook for the understanding of viral infection and I am really looking forward to its implementation at the ESRF".

References:

https://www.frm.org/fr/actualites/portrait-juan-reguera.

Kril, V., et al., Nat Commun 15, 8106 (2024).  https://www.nature.com/articles/s41467-024-51952-z.

Jones, R. et al.,  PNAS, 120 (12) e2213934120 https://www.pnas.org/doi/10.1073/pnas.2213934120

Jones, R. et al., Nature 589, 615-619 (2021); https://doi.org/10.1038/s41586-020-3036-8

Text by Montserrat Capellas Espuny

Top image: Juan Reguera. Credits: Julie Bourges.