Activities per year
The decoration of proteins by carbohydrates is essential for eukaryotic life yet heterogeneous due to a lack of biosynthetic templates. This complex carbohydrate mixture-the glycan profile-is generated in the compartmentalized Golgi, in which level and localization of glycosylation enzymes are key determinants. Here, we develop and validate a computational model for glycan biosynthesis to probe how the biosynthetic machinery creates different glycan profiles. We combined stochastic modeling with Bayesian fitting that enables rigorous comparison to experimental data despite starting with uncertain initial parameters. This is an important development in the field of glycan modeling, which revealed biological insights about the glycosylation machinery in altered cellular states. We experimentally validated changes in N-linked glycan-modifying enzymes in cells with perturbed intra-Golgi-enzyme sorting and the predicted glycan-branching activity during osteogenesis. Our model can provide detailed information on altered biosynthetic paths, with potential for advancing treatments for glycosylation-related diseases and glyco-engineering of cells.
Bibliographical noteCopyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
- COG complex
- glycan processing
- Golgi apparatus
- Markov chain Monte Carlo
- mass spectrometry
A computational model linking the organization of the mammalian glycosylation machinery with glycan processing
Dani Ungar (Chair)9 Nov 2020
Activity: Talk or presentation › Oral presentation
Dani Ungar (Chair)6 Mar 2019
Activity: Talk or presentation › Invited talk