Team "Translation regulation in normal and pathological conditions" *

Any injury to the central nervous system (CNS) leads to irreversible losses of cognitive, sensory, and/or motor functions. This can occur in the case of traumatic injuries, such as road accidents, or chronic injuries with the increase in neurodegenerative diseases. Indeed, CNS neurons are unable to reform a circuit because they cannot regenerate their axons after an injury. This will result in their death in most cases. Understanding the molecular mechanisms of neuroprotection and regeneration is, therefore, a major scientific and public health challenge aimed at developing innovative therapies since, to this day, no treatment is available.

The team's projects analyze neuroprotection and regeneration from different perspectives:

Regeneration, Ribosomes, and Translational Control
It is now widely recognized that the levels of mRNA and proteins are not correlated in cells. Cells use translational control to regulate the expression of key proteins at specific moments in the cell's life. Thus, several studies emphasize that translational regulation is at least as important as transcriptional regulation. Similarly, it is increasingly clear that the translational complex, particularly the ribosome, is directly involved in selecting mRNA to translate into protein and the amount of protein to synthesize. These recent discoveries have upended the dogma that the ribosome was neutral in translation, merely facilitating protein synthesis without intervening in its regulation. This also suggests that previous studies, by focusing solely on mRNA regulation, analyzed only a part of the mechanisms occurring during development and injury. Our team aims to determine the exact role of translation and the translational complex in the processes of neuroprotection and/or regeneration in the central and peripheral nervous systems. Our work seeks to highlight the existence of a "specialized" ribosome for regeneration, suggesting that the ribosome can modify its composition (RNA and/or protein) to directly regulate the mRNAs to translate.

Identification of Cellular Pathways Controlling Regeneration
In parallel with analyzing the impact of translation on circuit reformation, we are also interested in the major cellular pathways that can control regeneration mechanisms in the nervous system. We develop numerous high-throughput analyses (RNAseq transcriptomics, quantitative proteomics) and bioinformatics analyses to determine the signaling pathways involved during development or in adults after an injury.

Translational Approach to Promote Regeneration
The ultimate goal of our work is to promote in vivo regeneration in patients' nervous systems to enable circuit reformation and the return of lost functions. Based on our work, we have initiated innovative strategies to bring our best fundamental research targets to applied research and drug development. We currently have three projects:

• Creation of a Peptide Mimic Bank for CNS Regeneration: This project, in collaboration with the teams of Homaira Nawabi (GIN) and Sabine Chierici (DCM), aims to create a bank of peptide mimics based on the best candidates identified in our previous projects. We have established a screening method ranging from embryonic neuron cultures to in vivo survival/regeneration tests to select the best peptides and generate drug candidates.
• Nanoparticles, Magnetic Fields, and Regeneration: In collaboration with Bernard Dieny (SPINTECH, CEA), we are developing and using new magnetic particles to promote regeneration in the CNS, particularly in the spinal cord.
• Neuro-implant and Circuit Formation: In collaboration with the teams of Homaira Nawabi and Clément Hebert, we are developing a project on using neuro-implants and electrical stimulation to enable circuit reformation and functional recovery.