DECIPHERING SIALIC ACID O-ACETYLATION

• Applicant: Privatdozentin Dr. Martina Mühlenhoff
• Subject Area: Cell Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409784463

The aim of this proposal is to investigate the impact of sialic acid O-acetylation on kidney development and function by using novel genetic mouse models. O-Acetylation significantly contributes to the structural diversity of sialoglycans, but its function in vivo remains poorly understood. In preliminary work, we demonstrated that genetic ablation of the murine sialate O-acetyltransferase CASD1 results in a complete loss of 9-O- and 7,9-O-acetylated sialoglycans and causes a renal tubular 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. By functional assessment of rare, patient-derived CASD1 variants, we will investigate whether CASD1 is a novel candidate gene for human kidney disease. 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.

• DFG Programme: Research Units
• Subproject of: FOR 2953: Sialic Acid as Regulator in Development and Immunity