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The CNRGH is the French national research center which enables a response to scientific questions necessitating high throughput sequencing and genotyping thanks to the development and deployment of innovative integrated technologies. The organization of the CNRGH enables optimization of genetic and genomic research on human diseases by creating indispensable links between cohort constitution (DNA samples), identification of the responsible genes, and study of the transcriptome and epigenome.
List of the main projects of the Institut de Génomique
The work is a response to the very general issue of the gulf opening up between the discovery of proteins by new sequencing technologies, the number of which is growing exponentially, and their functions which are only slowly being determined. The complexity may be reduced by grouping the proteins in families to which functions are allocated on the basis of annotation of a few of the members. But the function of certain families remains mysterious. However, they represent an important potential for new functions and are worthy of special interest.
In order to further elucidate the families, the researchers use contextual and structural information together with experimental analyses. Prior work on the fermentation of lysine oriented the choice of a family of proteins of unknown function (DUF849). The team first identified the function of one of the members and determined its reaction mechanism by analysis of its 3-dimensional structure. The approach deployed is based on high-throughput experimental screening on representatives which were judiciously selected on the basis of 3-dimensional structural modeling and study of their genetic environments. Applied to DUF849, the method enabled discovery of a large number of activities certain of which were related to a metabolic context. The approach also enabled annotation of the function of the members of the family on the basis of structural motifs.
Laboratories involved: Laboratory of Bioinformatics Analyses for Genomics and Metabolism, Laboratory of Organic Chemistry and Biocatalysis, Laboratory of Genomics and Biochemistry of Metabolism, Laboratory for Cloning and Screening Bioconversion Activities.
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.