Description
Date depot: 13 juin 2022
Titre: Large-scale assessment of the impact of protein sequence variations on ageing using Drosophila melanogaster
Directrice de thèse:
Elodie LAINE (LCQB)
Directeur de thèse:
Michael RERA (SEED)
Domaine scientifique: Sciences et technologies de l'information et de la communication
Thématique CNRS : Sciences de l’information et sciences du vivant
Resumé: With the advent of high-throughput sequencing technologies, we have now access to large amounts of genomics and transcriptomics data. Yet, understanding the relationship between sequence variations and some specific phenotype remains an open challenge. Here, we propose to tackle this problem by combining high-throughput computational approaches with top notch experimental techniques using Drosophila as our model system. We will systematically predict the full single-mutational landscapes of all proteins annotated in Drosophila and will make the created knowledge base accessible to the community. Taken together with a novel theoretical framework for ageing, the two-phase ageing model, that helped us strongly improving the genomic signal for ageing in flies, we will identify a set of SNPs likely relevant to ageing and will validate their role in vivo with genome editing for engineering short-lived drosophila strains into long-lived ones. We will extend our analysis to sequence variations produced by alternative splicing. By combining evolutionary and (3D-) structural characterisation, we will identify a set of splice variants differentially expressed at different ages and/or whose expression is tightly regulated in the end-of-life process. Beyond such identification, we will develop a predictive model for the rewiring of their interactions. We expect this project to provide a valuable resource on the protein sequence-function relationship in Drosophila and to bring new insight about the key players of ageing.
Doctorant.e: Abakarova Marina