This proposal is a competing renewal for the NIGMS P41 National Center for Biomedical Glycomics. Glycomics can be defined in several ways, but in terms of our Center, we define Glycomics as the study of glycans, glycoconjugates, the proteins that regulate their expression, and the proteins that recognize them;in particular, we are interested in developing tools to facilitate learning how these molecules change during early embryonic development and during the onset of disease as a result of mutations that affect glycan expression. To develop technologies that will impact the understanding and regulation of the diversity of glycosylation, therefore, we felt it necessary to focus on Glycomics from more of a Systems Biology approach: investigation of glycosylation in a particular biological context, analysis of the fine details of glycan expression on glycoconjugates produced in specific cell types, identification of the glyco-genes that participate in glycan biosynthesis and the biosynthetic pathways that the enzymes and transporters expressed from the glyco-genes constitute. The structure of the Resource is focused on four Technological Research &Development programs plus Analytical Service and Training: TR&D1: Stem Cell and Induced Pluripotent Stem Cell (IPSC) Resources;TR&D2: Glycomics and Glycoproteomics;TR&D3: Transcriptome and Glycome Regulation;TR&D4: Glycobioinformatics. Our Center lists 31 DBPs, 73 Collaborative Projects, 192 Service projects, and four Courses/Workshops that have had 245 participants over the last four years. We also report 83 publications resulting from research associated with the Center. We have developed technologies in each of our TR&D that have significantly impacted the biomedical research community, and our over-arching goal is to amplify that impact over the next funding period.
The study of Glycomics is in its early stages and is very dependent on the development of tools and technologies. Glycomics involves types of molecules called glycans that are on the surfaces of cells which regulate many physiological processes such as inflammation and innate immunity. We have developed tools to assist biomedical researchers in understanding the structure and functions of these fascinating biomolecules.
|Chen, Yu; Bensing, Barbara A; Seepersaud, Ravin et al. (2018) Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii. J Biol Chem 293:5360-5373|
|Gas-Pascual, Elisabet; Ichikawa, Hiroshi Travis; Sheikh, Mohammed Osman et al. (2018) CRISPR/Cas9 and glycomics tools for Toxoplasma glycobiology. J Biol Chem :|
|Saeui, Christopher T; Nairn, Alison V; Galizzi, Melina et al. (2018) Integration of genetic and metabolic features related to sialic acid metabolism distinguishes human breast cell subtypes. PLoS One 13:e0195812|
|Spiciarich, David R; Oh, Stephen T; Foley, Amy et al. (2018) A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia. Cancer Res 78:6762-6770|
|Ferreira, Carlos R; Xia, Zhi-Jie; Clément, Aurélie et al. (2018) A Recurrent De Novo Heterozygous COG4 Substitution Leads to Saul-Wilson Syndrome, Disrupted Vesicular Trafficking, and Altered Proteoglycan Glycosylation. Am J Hum Genet 103:553-567|
|Talabnin, Krajang; Talabnin, Chutima; Ishihara, Mayumi et al. (2018) Increased expression of the high-mannose M6N2 and NeuAc3H3N3M3N2F tri-antennary N-glycans in cholangiocarcinoma. Oncol Lett 15:1030-1036|
|Sun, Lina; Ishihara, Mayumi; Middleton, Dustin R et al. (2018) Metabolic labeling of HIV-1 envelope glycoprotein gp120 to elucidate the effect of gp120 glycosylation on antigen uptake. J Biol Chem 293:15178-15194|
|Moremen, Kelley W; Ramiah, Annapoorani; Stuart, Melissa et al. (2018) Expression system for structural and functional studies of human glycosylation enzymes. Nat Chem Biol 14:156-162|
|Itoh, Kazuyoshi; Akimoto, Yoshihiro; Kondo, Shu et al. (2018) Glucuronylated core 1 glycans are required for precise localization of neuromuscular junctions and normal formation of basement membranes on Drosophila muscles. Dev Biol 436:108-124|
|Tanigaki, Keiji; Sacharidou, Anastasia; Peng, Jun et al. (2018) Hyposialylated IgG activates endothelial IgG receptor Fc?RIIB to promote obesity-induced insulin resistance. J Clin Invest 128:309-322|
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