The Role of O-GlcNAcylation in Intestinal Homeostasis: OGT Function in the Colonic Epithelium

How does an intracellular glycosylation-related modification influence the sugars displayed on intestinal cells and their interactions with the surrounding environment?

The intestinal epithelium forms an essential interface between the human body and the gut microbiota. Maintaining this barrier requires coordinated regulation of cellular metabolism, glycosylation, immune responses, and microbial interactions. One important regulatory mechanism is O-GlcNAcylation, a reversible modification in which a single N-acetylglucosamine residue is attached to intracellular proteins. This process is catalyzed by O-GlcNAc transferase (OGT) and is closely connected to cellular nutrient availability through the shared metabolic precursor UDP-GlcNAc. While intracellular O-GlcNAcylation is known to influence cellular signaling and metabolism, its effects on the more complex glycans present at the epithelial cell surface remain insufficiently understood. Victória investigates these relationships using a colon-specific OGT-deficient mouse model, allowing her to study the consequences of disrupted O-GlcNAcylation in the colonic epithelium.

Research Approach

Her project integrates several complementary approaches to investigate intestinal glycosylation, metabolism, and epithelial function.

1. 1. Investigating the role of OGT in intestinal epithelial cells

   1. Using genetic and molecular approaches, Victória examines the consequences of OGT deficiency for intracellular O-GlcNAcylation and the expression of glycosylation-related enzymes.

2. 2. Characterizing extracellular glycosylation

   1. At the SUGAR Lab, she will investigate whether changes in intracellular O-GlcNAcylation are accompanied by alterations in cell-surface glycosylation. High-resolution mass spectrometry-based glycomics, including CE-MS approaches, will be used to characterize glycan profiles in intestinal epithelial samples.

3. 3. Exploring spatial glycan organization

   1. By combining tissue microdissection with MALDI-based mass spectrometry approaches, the project aims to characterize glycosylation patterns in defined regions of colonic tissue. This spatial perspective may reveal whether alterations in glycosylation are associated with specific epithelial structures or tissue regions.

4. 4. Connecting glycosylation with intestinal function

Glycomics findings will be integrated with molecular and functional measurements of epithelial barrier integrity, intestinal metabolism, and microbiota-related changes.

Scientific Relevance

This project addresses an important connection between intracellular metabolic regulation and the complex glycans displayed on epithelial cell surfaces. By investigating how the OGT–O-GlcNAcylation axis influences extracellular glycosylation, Victória aims to improve our understanding of how intestinal cells maintain their barrier function and communicate with their environment. The findings may contribute to a better understanding of molecular mechanisms associated with inflammatory and metabolic intestinal diseases.