The role that diet plays in brain development will be probed by determining the components of the brain that are directly impacted by nutrition. Human milk is highly glycosylated containing short oligosaccharide chains that are more abundant than proteins. In early nutrition, there is a big burden on diet to accommodate the rapidly developing brain. The brain is rich in sialic acids, which are involved in neuronal outgrowth thereby creating synaptic connectivity through cell-cell interactions that in turn create memory. Human milk oligosaccharides are rich in sialic acids. It has long been proposed that sialic acids in human milk are an important source of sialic acids in the brain. However, the compounds in the brain that incorporate the exogenous sialic acids are not known, although they are generally believed to include proteins and lipids. This research will determine with high specificity the glycoconjugates in the brain that incorporate exogenous monosaccharides, particularly those from human milk oligosaccharides during the normal course of breast- feeding. A method combining advanced separation, mass spectrometry and chemical biology will be developed to determine the glycan structures, the glycoprotein, and the glycolipid involved in the incorporation of glycans from breast milk. Structural heterogeneity will be determined with lipid-specific characterization. Glycans in glycoproteins will be determined with structural heterogeneity at the site-specific level for both N- and O- glycosylation sites. We will develop deep glycomics tools to probe the glycoconjugates as glycoproteins and glycolipids that incorporate components from human milk. Determining the specific protein and lipid glycoconjugates that incorporate milk oligosaccharides would provide the most direct link between nutrition and brain development. 1

Public Health Relevance

RESEARCH NARRATIVE The effect of diet on brain development will be examined by determining the fate of oligosaccharides from human milk in brain glycoconjugates. A systems glycomic approach will be developed and employed to determine the specific glycoconjugates that incorporate the components of the human milk oligosaccharides. 1

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM049077-25
Application #
9850129
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Wu, Mary Ann
Project Start
1993-05-01
Project End
2021-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
25
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Park, Diane Dayoung; Xu, Gege; Wong, Maurice et al. (2018) Membrane glycomics reveal heterogeneity and quantitative distribution of cell surface sialylation. Chem Sci 9:6271-6285
Ruhaak, L Renee; Xu, Gege; Li, Qiongyu et al. (2018) Mass Spectrometry Approaches to Glycomic and Glycoproteomic Analyses. Chem Rev 118:7886-7930
Kailemia, Muchena J; Xu, Gege; Wong, Maurice et al. (2018) Recent Advances in the Mass Spectrometry Methods for Glycomics and Cancer. Anal Chem 90:208-224
Galermo, Ace G; Nandita, Eshani; Barboza, Mariana et al. (2018) Liquid Chromatography-Tandem Mass Spectrometry Approach for Determining Glycosidic Linkages. Anal Chem 90:13073-13080
Kailemia, Muchena J; Wei, Wanghui; Nguyen, Khoa et al. (2018) Targeted Measurements of O- and N-Glycopeptides Show That Proteins in High Density Lipoprotein Particles Are Enriched with Specific Glycosylation Compared to Plasma. J Proteome Res 17:834-845
Wong, Maurice; Xu, Gege; Park, Dayoung et al. (2018) Intact glycosphingolipidomic analysis of the cell membrane during differentiation yields extensive glycan and lipid changes. Sci Rep 8:10993
Song, Ting; Chen, Peng; Stroble, Carol et al. (2018) Serum glycosylation characterization of osteonecrosis of the femoral head by mass spectrometry. Eur J Mass Spectrom (Chichester) 24:178-187
Phoomak, Chatchai; Silsirivanit, Atit; Park, Dayoung et al. (2018) O-GlcNAcylation mediates metastasis of cholangiocarcinoma through FOXO3 and MAN1A1. Oncogene 37:5648-5665
Miyamoto, Suzanne; Stroble, Carol D; Taylor, Sandra et al. (2018) Multiple Reaction Monitoring for the Quantitation of Serum Protein Glycosylation Profiles: Application to Ovarian Cancer. J Proteome Res 17:222-233
Krishnan, Sridevi; Shimoda, Michiko; Sacchi, Romina et al. (2017) HDL Glycoprotein Composition and Site-Specific Glycosylation Differentiates Between Clinical Groups and Affects IL-6 Secretion in Lipopolysaccharide-Stimulated Monocytes. Sci Rep 7:43728

Showing the most recent 10 out of 102 publications