Laureats

Key words: Spinal Cord, MRI, Amyotrophic Lateral Sclerosis, (Ultra) High Field, Longitudinal
Follow-up

This project focuses on the evaluation of early tissue impairment encountered in the context of Amyotrophic Lateral Sclerosis by taking advantages of potentialities offered by both ultra-high field Magnetic Resonance Imaging (7T) and electrophysiological measurements. The project is based on the already existing close collaboration between CRMN-SLA (Pr. S. Attarian and Dr. A. Verschueren) and CRMBM-CEMEREM (V. Callot’s team).

Cardiomyopathies are an important cause of heart failure and sudden cardiac death. Little is known about the role of rare genetic variants in inflammatory cardiomyopathy. Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory cardiomyopathy prevalent in Latin America, developing in 30% of the 6 million patients chronically infected by the protozoan Trypanosoma cruzi, while 60% remain free of heart disease (asymptomatic (ASY)). The cytokine interferon-γ and mitochondrial dysfunction are known to play a major pathogenetic role. Chagas disease provides a unique model to probe for genetic variants involved in inflammatory cardiomyopathy.

The development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic ribonucleic acids. They are ubiquitous genetic elements conserved across species and suspected to be involved in numerous cellular processes. MetamORF (https://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing them and summarizing redundant information, we were able to identify a total of 1 162 675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data have been reprocessed using a normalized nomenclature. MetamORF enables new analyses at locus, gene, transcript and ORF levels, which should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs can be searched starting from a gene, a transcript and an ORF ID, looking in a genome area or browsing the whole repository for a species. The database content has also been made available through track hubs at UCSC Genome Browser. Finally, we demonstrated an enrichment of genes harboring upstream ORFs among genes expressed in response to reticular stress.