SMNuHoMICS Project

Unraveling the Role of SMN in Nucleolar Homeostasis and Spinal Muscular Atrophy

About the project

SMNuHoMICS is an international research initiative exploring how the SMN protein safeguards nucleolar function and how its dysfunction contributes to Spinal Muscular Atrophy (SMA). By combining cutting-edge omics approacheswith expertise from France, Canada, and Belgium, the consortium aims to uncover new molecular mechanisms and open the way to future diagnostic and therapeutic strategies for SMA.

SMNuHoMICS is an international research initiative exploring how the SMN protein safeguards nucleolar function and how its dysfunction contributes to Spinal Muscular Atrophy (SMA). By combining cutting-edge omics approaches with expertise from France, Canada, and Belgium, the consortium aims to uncover new molecular mechanisms and pave the way for future diagnostic and therapeutic strategies for SMA.

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disease caused by mutations in the SMN1 gene, leading to reduced levels of the Survival of Motor Neuron (SMN) protein. While SMN is best known for its role in motor neuron survival, it is a multifunctional protein involved in many essential cellular processes. Recent discoveries by our consortium have revealed that SMN also plays a crucial role in the reorganization of the nucleolus—the cell’s ribosome factory—particularly following DNA damage and repair.

The SMNuHoMICS project brings together an international team of experts to investigate how SMN contributes to nucleolar homeostasis and how its dysfunction influences the pathophysiology of SMA. Using complementary omics approaches (transcriptomics, proteomics, and interactomics), we aim to determine how SMN regulates ribosomal RNA modifications, protein interactions, and nucleolar dynamics under stress conditions.

Our scientific objectives are to:

• Validate the newly identified nucleolar functions of SMN in motor neuron models
• Investigate how ribosomal and spliceosomal RNA modifications are altered in SMA cells following DNA damage
• Define the network of SMN protein partners and their regulation by post-translational modifications

Consortium partners

• France – Dr. Ambra Giglia-Mari, Institute NeuroMyoGene (INMG), CNRS, Project Coordinator
• Canada – Dr. Jocelyn Côté, Department of Cellular and Molecular Medicine, University of Ottawa
• Belgium – Dr. Denis Mottet, GIGA Research Institute, University of Liège

Fundings

The SMNuHoMICS project is supported under the JPND (EU Joint Programme – Neurodegenerative Disease Research) call for proposals on large-scale analysis of omics data for drug-target discovery in neurodegenerative diseases.

Thanks to the program Ambition International of Région Auvergne-Rhône-Alpes and the IRP Inserm to finance the exchanges and travels of this program.