Typologie d'actualités: Group Cell Signalling

La ligue contre le Cancer (The League Against Cancer) supports research carried out at the CBM

Each year, the Grand Ouest Committee of the League Against Cancer actively participates in research by financing a certain number of scientific projects. At the start of 2024, he donated €84,000 to CBM researchers.

3 projects, at the cutting edge of cancer research, have been funded.

"New therapeutic approach in oncology: development of PROTACs targeting LIMK1 and LIMK2 kinases"
Leader: Béatrice Vallée co-leader of the “Cell signaling and neurofibromatosis” team
Partner: Karen Plé, ICOA, UMR7311, CNRS/University of Orléans

The protein kinases, LIMK1 and LIMK2, are involved in cell skeletal remo Their active role in the development of cancers has been shown both in the formation of tumors and in their dissemination and the growth of metastases. Targeting LIMK1 and LIMK2 to develop new anti-cancer therapies is therefore a very relevant strategy.Unfortunately, traditional small chemical molecules inhibiting the activity of LIMK1 and LIMK2 have not passed clinical trials.In our project, we therefore decided to develop a new class of molecules, PROTACs, which allow the destruction of their target directly in the cell. In our case, we target the destruction of LIMK1 and LIMK2 to annihilate their oncological activity. This PROTAC strategy is very innovative and growing. Building on very promising results that have been obtained on other therapeutic targets, we hope to demonstrate the proof of concept of this new approach targeting LIMK1 and LIMK2, and thus open the way to new therapeutic molecules.

This project received the support of the League against Cancer, the Committees of Loiret, Loir-et-Cher and Morbihan, for the sum of €32,000.

“Innovative prostate cancer diagnosis for personalized medicine approaches: intelligent multiplex mapping of SKCa channels using near-infrared emitting lanthanide-based metallacrowns”
Leader: Svetlana ELISEEVA, “Luminescent lanthanide compounds, spectroscopy and optical bioimaging” team

Each patient's tumors are different because each individual is different. It is therefore crucial to take this diversity of tumors into account to develop personalized approaches. Our research work aims to characterize cancerous tumors with the aim of providing more effective treatment to cure cancer.Several specific potassium channels play a major role in the progression of cancerous tumors and are sensitive to therapies. In this project, we are implementing an innovative near-infrared optical imaging approach which will make it possible to establish the precise identity map of these potassium channels for each patient in order to provide personalized treatment.

This project received the support of the League against Cancer of the Committees of Loiret, Loir-et-Cher and Sarthe, for the sum of €30,000.

“Cancer immunotherapy: evaluation of synthetic versus in-cell expressed bispecific di-affibodies”
Leader: Josef Hamacek, head of the “Molecular assemblies and complex systems” team
Partners: Federico Perche, Vincent Aucagne (CBM), Florence Velge-Roussel (NMNS Tours)

Several receptors on the surface of cancer cells may represent potential targets for antibodies with broad neutralization spectrum. The principle of bispecific synergistic antibodies is to bind via a binding site on the surface of the tumor cell and with the other site to a receptor on the surface of the immune effector cell (NK, T lymphocytes).In this context, antibodies can be replaced by affibodies (AfBs) presenting affinities and selectivities for their targets comparable to antibodies, but having smaller size.This project aims to develop bispecific di-AfBs as innovative agents for the diagnosis and immunotherapy of cancer.These complex molecules are made up of two AfBs linked by linkers and can thus target two epitopes. AfBs will bind specifically to the corresponding receptors overexpressed on the surface of cancer cells to block signaling pathways, and to promote the recruitment of effector cells.This concept offers new therapeutic perspectives and makes it possible to optimize interactions with the cell and provoke the immune reaction.

This project received support from the League Against Cancer of the Committees of Loiret, Sarthe and Côtes d’Armor, for the sum of €22,000.

Truly life materials?

Physiological characterization of life in Engineered Living Materials by confocal microscopy at single cell resolution.

The CNRS Institute of Chemistry reported this remarkable research on its site. See the article

Engineered Living Materials (ELMs) combine living cells with non-living scaffolds to get life-like characteristics, such as biosensing, growth, and self-repair. Some ELMs are 3D-printed, and called bio-ink. For ELMs to be functional, cells in ELMs has to remain alive and active. However, currently, microorganism physiology in ELMs is still elusive and restrict their use.

Researchers of the team "Cell signalling and neurofibromatosis" reconstituted such bioprinted ELMs by associating the yeast Saccharomyces cerevisiae with the hydrogel Pluronic F-127. Theydeveloped genetically engineered yeast by integrating fluorescent gene whose expression is correlated to a physiological parameter: ATP concentration (metabolism), intracellular pH (growth phase), morphology … These engineered and ratiometric biosensors are effective and allow to assess yeast physiological status in ELM directly in situ by confocal microscopy at single cell scale level. They constitute a valuable tool easy to adapt to any other system by associating them to other materials to evaluate their biocompatibility.

Furthermore, the researchers tested their recently developed copper biosensor embedded into this hydrogel F-127, and showed it is fully functional into this ELM. Yeast biosensor association with hydrogel provides several very interesting advantages such as protecting yeast from contaminations and supplying them with nutrients.

This work allows to establish the proof of concept that F127 associated with engineered yeast S. cerevisiae is a promising ELM in order to develop easy to use whole-cell biosensors able to detect copper directly on samples collected in the environment.

Bojan Žunar B., Ito T., Mosrin C., Sugahara Y., Bénédetti H., Guégan R. and Vallée B.
Confocal imaging of biomarkers at a single-cell resolution: quantifying 'living' in 3D-printable engineered living material based on Pluronic F-127 and yeast Saccharomyces cerevisiae.
Biomater Res 26, 85 (2022). https://doi.org/10.1186/s40824-022-00337-8

CBM PhD students have talent!

Ons Kharrat, from the "NMR of Biomolecules" group, received one of the 3 prizes for the best oral communication at the GDR MuFoPAM days which took place from October 19 to 21, 2022.
This prize was awarded to him by the company Genepep (https://www.genepep.com/accueil/).

Elodie Villalonga, from the "Cell signaling and neurofibromatosis" group, won one of the 2 prizes for the best oral communication
and
Valentin Beauvais, from the group “Dysregulation of autophagy during inflammation due to HIV”, received one of the poster prizes at the 34th Biotechnocentre conference which took place on October 20 and 21, 2022.

A unique biosensor able to detect as low as 10 nM bioavailable copper based on whole-cell eukaryotic Saccharomyces cerevisiae

Cooper in a micronutrient essential to life, its lack induces neurological and blood disorders. It is extensively used in industry, in particular in the batteries of electric cars, but also as a fertilizer and fungicide. However, it is toxic at high concentrations, and is considered as a critical emerging pollutant. Copper detection in water constitutes a major societal and environmental issue.

Currently, copper concentrations are monitored by sophisticated analytical methods requiring time, expansive equipments and deep expertises. Moreover, these technics quantify total copper present in a sample and not copper interacting with living organisms.

Researchers of CBM developed a new and atypical device able to detect copper in a very sensitive and easy way. Their biosensor is based on whole-cell eukaryotic living Saccharomyces cerevisiae, allowing detection of bioavailable copper. It is a ratiometric biosensor, measuring the ratio between (i) a constitutively expressed fluorescent protein and (ii) another fluorescent protein whose expression is directly correlated with copper concentrations as its expression is in under the control of CUP1 promoter, a well-known promoter in Saccharomyces.

By genetic engineering, researchers created many different variants to optimize the response of our biosensor. Their best biosensor is able to detect as low as 10 nM of copper in a linear range from 10-3 to 10-8 M, much better features compared to other currently reported whole cell copper biosensors. This biosensor was also validated on “real” samples: detected concentrations are totally in agreement with manufacturers’ values.

Reference of the article :
Bojan Zunar, Christine Mosrin, Hélène Bénédetti, Béatrice Vallée
Re-engineering of CUP1 promoter and Cup2/Ace1 transactivator to convert Saccharomyces cerevisiae into a whole-cell eukaryotic biosensor capable of detecting 10 nM of bioavailable copper
Biosensors and Bioelectronics 214 (2022) 114502

The article was reported by the CNRS Institute of Chemistry on its website and in its letter "En direct des labos".

 

Biotechnocentre 33rd conference

The 33rd Biotechnocentre conference will be held on October 7 and 8, 2021  at Center Parcs Domaine Les Hauts de Bruyères - Rue Lamotte - 41 600 Chaumont-sur-Tharonne.

With the participation of Doctoral School 549 "Santé, Sciences Biologiques et Chimie du Vivant" (SSBCV).

Among the speakers announced, Vincent Aucagne, head of the thematic group "Synthetic proteins and bioorthogonal chemistry" " will give a conference entitled "Methodological developments for the chemical synthesis of proteins"

Registration before September 3, 2021 at biotechnocentre@sfr.fr

See the poster

Conferences program

A CBM project winner of the CNRS premature program

This project entitled "Preclinical Validation of LIMK Inhibitors in Cancer" will receive specific financial support. It is led by Hélène Benedetti, a researcher at the Center for Molecular Biophysics (CBM), and Sylvain Routier, a researcher at the Institute of Organic and Analytical Chemistry (ICOA). Its goal is to determine the efficacy of inhibitors, protein kinases LIMKs, new therapeutic targets particularly interesting to treat cancers for which existing therapies are ineffective. Prematuration will make it possible to characterize the cellular effect of these compounds and to determine their pharmacokinetic properties with a view to performing in vivo tests on three cancer models.