Modeling Glycan Processing Reveals Golgi-Enzyme Homeostasis upon Trafficking Defects and Cellular Differentiation

Peter Fisher, Hannah Spencer, Jane Thomas-Oates*, A. Jamie Wood, Daniel Ungar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1231-1243
Number of pages13
JournalCell reports
Issue number4
Publication statusPublished - 23 Apr 2019

Bibliographical note

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.


  • COG complex
  • glycan processing
  • Golgi apparatus
  • Markov chain Monte Carlo
  • mass spectrometry
  • MSCs

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