DOLITTLE - The evolution and role of protein N-linked glycosylation in the animal tree
Image credit: Fabian RupertiN-linked glycosylation is a complex post-translational modification in which (oligo)saccharides are covalently attached to extracellular and membrane-bound proteins. As such, N-glycoproteins are central to cell-cell and cell-ECM adhesion, recognition and communication, making them fundamental players in metazoan traits such as multicellularity, the immune and nervous systems, and interactions with symbionts, as found in corals, sponges and other marine species. Despite their importance, our understanding of the diversity and role of N-glycoproteins in Metazoa is currently poor, owing to sparse taxonomic sampling and the lack of universal analytical frameworks.
In this project, I am using use high-throughput, high-resolution mass spectrometry–based glycoproteomics to profile the N-glycoproteomes of ~30 opisthokont species spanning major evolutionary transitions from unicellular fungi and holozoans to non-bilaterian and bilaterian animals. In doing so, we provide the first site- and glycan-resolved N-glycoproteome for multiple phyla, including marine species such as choanoflagellates, ctenophores, sponges, and cnidarians, while also greatly expanding coverage for well-studied model species. Ongoing comparative analyses across orthologous glycoproteins aim to trace the emergence and conservation of glycosylation sites and attached glycans (and their classes), as well as their function and cell type-specificity.
The assembly and analysis of this expansive new resource will reveal how changes in the “glycan code of life” shaped the origin of animal multicellularity, the diversification of cell types and their intra- and interspecies interactions.
This project is a large collaboration between multiple labs, including but not limited to the lab of Bernard and Sandie Degnan (Univeristy of Queensland, Australia), the Schulz lab (University of Queensland, Australia), the Savitski lab (EMBL Heidelberg, Germany) and the Arendt lab (EMBL Heidelberg, Germany).
