# Systems Biology of Glycosylation

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $504,457

## Abstract

Glycosylation is among the most abundant post-translational modifications in mammalian cells. It decorates a
vast majority of mammalian proteins. Glycans absolutely control or finely-tune a number of cellular processes
in higher organisms including development, immunity, inflammation, bleeding and oncogenesis/metastasis.
Despite its biomedical importance, knowledge regarding the distribution of carbohydrates that decorate
different glycoconjugates (glycoproteins and glycolipids) in a site-specific manner is incomplete. Even less is
known about how these glycans change in response to biochemical signals or other perturbations. Further,
while basic knowledge of various glycosylation reactions are becoming available, systems-based tools to
integrate these data are less well-developed. Such integration is likely to be a key to understanding emerging
concepts that suggest that besides mediating simple molecular recognition/adhesive interactions, glycans are
also likely to be key regulators of cell signaling. Keeping these shortcomings in mind, we propose to perform a
series of studies to assay the impact of carbohydrates on human leukocyte-endothelial cell adhesion and
related signaling processes under conditions of inflammation. Specifically, the current proposal has a focus on
human cells only, since extensive studies performed in the previous funding cycle show that the post-
translational glycosylation machinery in humans is likely to exhibit key differences with other mammals, most
notably mice. Our overall hypothesis is that “Systems-level quantitative experiments and modeling can reveal a
more complete picture of the pathways controlling mammalian glycosylation. Such analysis can identify new
checkpoints/rate-limiting steps that control glycan-dependent human leukocyte-endothelial cell adhesion and
diapedesis.” The specific aims are: 1. To develop glycoProbes and related computational tools to rapidly and
quantitatively measure the glycosylation status of cells, under resting & stimulation conditions 2. To establish a
link between the cellular glycome & genome. Here, we test the hypothesis that the perturbation of the glycome
results in alterations in the cellular transcriptome and related functions. 3. To identify the glycosylating
enzymes regulating human leukocyte adhesion, signaling and transmigration across the endothelium. The
project involves collaboration between investigators with expertise in Systems Glycobiology based modeling
(Neelamegham), genomics (Buck), proteomics (Qu) and lipidomics (Atilla-Gokcumen). Experimental studies
span multiple scales from genes, to proteins/enzymes, to carbohydrate structure and cell adhesion/signaling
function. The computer modeling integrates this information to provide novel web-based tools for data analysis,
and the prediction of the effect of system perturbation on glycan structure and function. In the long-run, this
study may lead to the identification of critical regulators (transcripts/proteins...

## Key facts

- **NIH application ID:** 9932809
- **Project number:** 5R01HL103411-09
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** SRIRAM NEELAMEGHAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,457
- **Award type:** 5
- **Project period:** 2011-09-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932809

## Citation

> US National Institutes of Health, RePORTER application 9932809, Systems Biology of Glycosylation (5R01HL103411-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9932809. Licensed CC0.

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