Typologie d'actualités: Team Molecular, Structural and Chemical Biology

J.-M. Bonmatin co-organiser of the HOLIMITOX feedback day. Holimitox a network of 16 laboratories working on impacts of SDHI fungicides.

The report day of the Holimitox network (https://holimitox.fr/) was held on 7 November 2024 in Paris. The Holimitox interdisciplinary scientific network involves 16 national research laboratories, including the CBM, and has been working for four years on the impact of SDHI pesticides on the environment, biodiversity and health. Holimitox is financed solely by public funds or charitable foundations (>€2M).

The Institut d'Etudes Avancées de Paris hosted the event at the prestigious Hôtel de Lauzun on the Île Saint Louis. J.-M. Bonmatin, a member of the Holimitox Steering Committee, co-organised the two half-day events. The programme is available here. The morning was devoted to presenting the scientific results. The afternoon was devoted to putting these results into perspective within the broader issue of pesticides, this through three round-table discussions. All the stakeholders (parliamentarians, universities and research bodies, ministries (health, agriculture, ecology), ANSES, ANR, manufacturers, journalists, manufactures, NGOs, lawyers, charitable foundations, etc.) played to a full house.

 

 

A new anticancer therapeutic strategy targeting the protein kinases LIMKs via new innovative chemical compounds

These last years, significant advances have been obtained in oncology leading to an increase of patients’ lifespan and improved life conditions. However, several cancers remain difficult to treat with mitigated results, and more and more resistances are observed. It is then vital to go on developing new therapies.

LIM kinase proteins are overproduced in many cancers and constitute interesting therapeutic targets. All over the world, small chemical molecules targeting their kinase activity have been developed these 15 last years, but failed to reach clinical trial stage. In collaboration with chemists from ICOA Institute, we developed a new category of innovative small molecules, called PROTACs, which aims to decrease or even to totally shut down the production of LIM kinase proteins. Our first results are really promising as 2 of the molecules synthesized by the chemists are very active: they totally shut down LIMK production and exhibit drastic effects on cells. We have to go on with the characterization of these molecules especially their cellular effect to open the path towards a new innovative efficient therapeutic strategy targeting the LIM kinase proteins for cancer treatment.

A new regulatory mechanism involved in the bacterial response to cold shock

Cold shock is a common stress for bacterial pathogens inhabiting warm-blooded hosts. It occurs upon abrupt release from the host into the comparatively cold environment. Understanding how pathogens cope with cold shock is crucial to define how they survive on contaminated surfaces and spread to new hosts.

The‘RNA remodeling’ team and I2BC colleagues discovered that transcription termination factor Rho is a crucial player in the bacterial cold shock response (CSR), challenging the prevalent view that the CSR is mostly a posttranscriptional program. Temperature-sensing mRNA switches either allow (at 37°C) or prevent (at 15°C) Rho-dependent termination of the transcription of cold shock genes. During cold acclimation, the cold shock proteins accumulate until they bind to their mRNAs and switch them back into conformations prone to Rho action, thereby providing negative feedback control of their own expression. This regulatory loop works alongside the established posttanscriptional mechanisms to ensure tight and quick regulation of the cold shock genes.

This discovery published in the journal Molecular Cell illustrates the complexity of the bacterial stress responses and highlights Rho as a promising therapeutic target. It was reported by CNRS Chimie on its website.

Référence :
Rho-dependent transcriptional switches regulate the bacterial response to cold shock
Mildred Delaleau, Nara Figueroa-Bossi, Thuy Duong Do, Patricia Kerboriou, Eric Eveno, Lionello Bossi, & Marc Boudvillain*
Molecular Cell https://doi.org/10.1016/jmolcel.2024.07.034