P7 - Deciphering sialic acid O-acetylation

Sialic acids (Sias) show a pronounced structural diversity that arises from post-synthetic modifications of a shared nine-carbon sugar backbone. The Mühlenhoff lab has identified CASD1 as key enzyme in the biosynthesis of 9-O-acetylated sialoglycans and setup a unique O-acetylation specific toolbox. In preliminary work, we demonstrated that genetic ablation of CASD1 in mice results in a complete loss of 9-O- and 7,9-O-acetylated sialoglycans and causes a kidney phenotype. To understand how sialic acid O-acetylation contributes to kidney integrity, we will perform functional assays on isolated primary cells and explore the contribution of O-acetylated sialoglycans on tubular epithelial and vascular endothelial cells through the generation of cell type-specific Casd1 knockout mice. In parallel, we will pursue studies to unravel the interplay of CASD1, sialyltransferases and the catabolic sialate 9-O-acetylesterase SIAE in shaping the Sia O-acetylome. Within the research unit, our project is closely linked to projects 2, 5 and 9, and will benefit from specific interactions with projects 1, 6, and 8.