The broad goal of this competing renewal focuses on glycosaminoglycan separation, purification and complete chemical characterization as it pertains to heparin and HS complexation to various inflammatory chemokines. Methods will be developed to separate, purify and identify glycosaminoglycan (GAG) binders of three specific Rheumatoid Arthritis associated chemokines using chromatography, ion mobility mass spectrometry (IM-MS) and CID-MS. Complexation of GAG binders to their chemokine counterparts will be investigated by MS with the monomer, dimer and tetramer assemblies measured using IM-MS. These studies will be paired with the compositional analysis of GAG in sera from women with Rheumatoid Arthritis in the pre- and postmenopausal age range to determine health benefits of HRT and its correlation with GAG composition. The three specific aims are:
Specific Aim 1 : GAG composition in Human Serum, Specific Aim 2: Chromatographic preparation, separation, identification and complexation of GAG libraries with Chemokines, and Specific Aim 3: Ion Mobility MS and X-ray crystallography of Chemokine and GAG binders. The major areas proposed are interwoven in such a way that methods development, biotechnology and application to biologically relevant systems are the cohesive elements that bind the proposed research together.

Public Health Relevance

This research will develop methods to separate, purify and identify glycosaminoglycan (GAG) binders of various inflammatory chemokines using chromatography and ion mobility mass spectrometry (IMS). Complexation of these binders to their chemokine counterparts will be investigated by MS and multimeric assemblies measured using theoretical and experimental collision cross sections via IMS. These studies will be paired with the compositional analysis of GAG in serum from Rheumatoid Arthritis women in the pre- and postmenopausal age range to determine health benefits of HRT and its correlation with GAG composition.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047356-21
Application #
8731901
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Edmonds, Charles G
Project Start
1992-05-01
Project End
2017-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
21
Fiscal Year
2014
Total Cost
$257,221
Indirect Cost
$80,558
Name
University of California Davis
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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