LID-PEG Project 4 will perform glycomic, glycoproteomic and glycogene transcriptome studies of human lung and inflammatory cells, focusing on the identification and regulation of siglec counter-receptors.
The history of discovery related to glycans that mediate inflammatory responses is rich with examples of endogenous ligands that have presented unanticipated complexity and specificity compared to initial leads. Identifying counter-receptor carrier molecules (protein and/or lipid) is an essential first-step toward unraveling siglec counter-receptor functions. Glycoproteomic and glycolipidomic characterization of counter-receptors and their carriers will frame future questions regarding the cell biology and biochemistry of counter-receptor presentation, recycling, clustering/surface-mobility, and the potential for parallel or reciprocal signaling through carrier-mediated pathways following siglec engagement.
We will apply our experience in the structural characterization of glycans by mass spectrometry (and other orthogonal methods) to identify siglec counter-receptors. We begin by characterizing the glycome and glycoproteome of two separable compartments of the human respiratory tract. We then focus on isolated human cell types that contribute to inflammation in order to assess specific sub-glycomes . We will also investigate the complex matrix of cellular signaling involved in lung inflammation to decipher which signals most effectively drive the expression of the glycans identified through our structural characterization, with special attention to siglec counter-receptors.
Dr. Michael Tiemeyer has developed enhanced analytical tools to perform glycomic and glycoproteomic analyses on small amounts of complex material. The highly efficient glycan analytic tools he developed for structural analyses in Drosophila are mature and are completely translatable to the glycomes and glycoproteomes of inflammatory cells and lung tissues. The combination of high sensitivity glycomic and glycoproteomic analyses with methods to probe the regulation of glycan expression in the inflammatory environment brings knowledge and capabilities that will be key to the success of this LID-PEG.
- University of Georgia
Complex Carbohydrate Research Ctr.
315 Riverbend Rd.
Athens, GA 30602-4712
- Phone: 706-542-2740