2012 — 2016 |
Baker, Erin S |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Platform Providing Increased Throughput, Sensitivity and Specificity For Metabolo @ Battelle Pacific Northwest Laboratories
DESCRIPTION (provided by applicant): The overall objective of this project is to develop and initially evaluate a novel multidimensional ion mobility- mass spectrometry based high throughput metabolomics platform and associated automated informatics pipeline for analyses of biomedically and clinically relevant samples that will provide measurements that will be: much more robust, provide greater coverage and sensitivity, be more than an order of magnitude higher throughput, and have higher quantitative utility compared to present platforms. The new platform will exploit new developments in ionization, ion funnel technology, multidimensional ion mobility separations, and mass spectrometry interfacing. Improvements to the speed of the bioinformatics pipeline will be achieved in part by creating accurate mass and time (AMT) tag databases that utilize information from the multidimensional ion mobility separations in conjunction with accurate mass information to effectively identify previously cataloged metabolites and enable broad quantitative comparisons for different samples. The initially unknown metabolites observed in these measurements can also be compared across sample sets, and in many cases other detected species also identified based on their accurate masses, MS/MS data, and structurally related ion mobility information, and thus driving a continued expansion of the metabolite AMT tag database. The new platform and informatics pipeline will be initially evaluated and demonstrated using significant sets of blood spot and serum samples, and rapidly disseminated to make the technology more broadly available.
|
0.915 |
2019 |
Baker, Erin S Maccoss, Michael Montine, Thomas J (co-PI) [⬀] Muddiman, David C. [⬀] |
R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Leveraging Glycomics to Characterize a Molecular Signature of Alzheimer's Disease @ North Carolina State University Raleigh
Mass spectrometry is an extraordinarily powerful bio-analytical technique that has had a profound impact on our molecular understanding of human health and disease. Major advances in mass analyzer technology, gas-phase separations, dissociation techniques, and ionization methods are largely attributed to the central role that mass spectrometry plays in the field of systems biology. While mass spectrometry has evolved over the last century into a highly effective analytical tool, there are still opportunities for new advances, allowing an even more diverse array of biological questions to be addressed. This proposal is centered on the development and characterization of novel, multi-functional, glycan- specific chemical tags for increased detection by spectroscopic (i.e., absolute quantification) and biological mass spectrometry (i.e., relative quantification) methods. Moreover, the establishment of gas- phase separations of glycans to overcome the isomer barrier challenge is essential to fully understanding the underlying biology. The short-term objective of this proposal is to develop and validate a library of novel multi-functional tags and ion mobility (IM) measurements to resolve glycan isomers, with the long-term goal being their application in an Alzheimer?s disease human tissue repository. This project will also develop open-source software for automated glycan analysis to facilitate accurate and high-throughput analysis, including the support of IM data. These N-glycan results will be combined with data on the glycoproteome and proteome, contributing to the ultimate goal elucidating glycans and glycoproteins for a deeper understanding of the role a key protein modification has in the development of AD. Public Description of Proposed Research Mass spectrometry (MS), the science related to the ?weighing of molecules?, has had a profound impact on the study of human health and disease including cancer, heart disease, neural development, and auto-immune diseases. However, this research will leverage front-end chemistries and gas-phase separations for MS-based glycomics/glycoproteomics to dramatically improve the ability of MS to detect, quantify, and resolve glycan isomers extracted from brain tissue proteins. This will address a more diverse array of contemporary biomedical questions including the quantification of diagnostic and prognostic biomarkers. This proposal is centered on the elucidation of a glycan-specific biomarkers and which proteins are modified for understanding the diagnosis and progression of AD. Another major benefit of this research will be to provide new drug targets (e.g., glycoproteins).
|
1 |