Description
Date depot: 9 juin 2023
Titre: Charting proteoform diversity across 800 million years of evolution
Directrice de thèse:
Elodie LAINE (LCQB)
Directeur de thèse:
Hugues RICHARD (LCQB)
Domaine scientifique: Sciences et technologies de l'information et de la communication
Thématique CNRS : Sciences de l’information et sciences du vivant
Resumé: The recent advances in high-throughput sequencing, imaging and proteomics have revealed an incredible complexity behind the classical protein sequence-structure-function paradigm. The vision of one gene coding for one protein folding into a unique 3D structure to perform a specific function is largely oversimplified. In particular in multicellular organisms, alternative splicing (AS) can produce several protein isoforms, or proteoforms, from the same gene. These proteoforms may in turn adopt different 3D shapes and interact with different cellular partners. In humans, there are about 100,000 known protein coding transcripts coming from 20,000 genes. The combinatorial space of possible interactions between them is huge. Hence, AS potential for expanding proteome diversity and rewiring interaction networks is fascinating. The goal of this doctoral project is to build a comprehensive description of proteoform diversity across hundreds of organisms spanning about 800 million years of evolution. The candidate will expand on a method and a graph-based data structure developed by the host team to summarize transcript diversity across many species. More specifically, they will conceive and develop an algorithm for mapping hundreds of genomes onto evolutionary splicing graphs. They will assess the link between evolutionary conservation and functional importance of the transcripts. The expected outcomes are a reliable and scalable computational framework for collating genomic, transcriptomic and proteomic evidence for protein diversity, and a knowledge base of functional proteoforms.
Doctorant.e: Carrel-Billiard Louis