Quantitative multi-omics atlas of the model chordate Ciona enables evolutionary insights into expression dynamics

Abstract

This thesis consists of two chapters, which study the control of protein dynamics during nutrient limitation and during embryogenesis. The first chapter delves into the role of GCN2 in adapting protein synthesis to conditions of limited amino acid availability. The study employs a genome-wide CRISPR-based screen in pancreatic cancer cells to illuminate the cellular machinery required for scavenging-driven growth. The findings reveal that in conditions of limited amino acid availability, cells must suppress translation inhibition by tuning mTORC1 activity or by activating GCN2. This minimizes ribosome stalling without suppressing overall protein synthesis. GCN2 also promotes the synthesis of catabolic proteins, critical for growth in amino-acid-poor conditions, enabling sustained growth by macropinocytosis - or using extracellular protein as an amino acid source. The second chapter presents a multi-omics atlas of the model chordate Ciona, covering eight developmental stages and ~7,000 genes at the protein and transcript level. When the data collected in the simple chordate was compared to the Xenopus vertebrate, we found higher evolutionary conservation of protein than of transcript dynamics. This supports an anti-hourglass model where developmental divergence across species is maximal around gastrulation. Together, this study presents a comprehensive proteome atlas in Ciona which provides a valuable resource for evaluating both cross-species conservation and species-specificity from simple chordate to vertebrate, highlighting post-transcriptional conservation.