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. Most common is 9-O-acetylation, which can mask the recognition site for Sia-binding proteins and impact ganglioside biology. Several lines of evidence point towards a role of Sia 9-O-acetylation in development and autoimmune signaling, but comprehensive insight is missing. 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 this project, we will investigate the murine Sia O-acetylome and generate Casd1 knockout mice to decipher the functional role of 9-O-acetylated sialoglycans in vivo. This will be complemented by cellular studies to unravel the interplay of CASD1, sialyltransferases and the catabolic sialate 9 O acetylesterase SIAE in shaping the Sia O-acetylome.