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National Center for Quantitative Biology of Complex Systems

Active date: 07/05/206-06/30/2026

In this TR&D, we will develop and apply a new class of isobaric tags for protein and protein post-translational modifications (PTMs) quantitation. Specifically, the tags will be built upon an amine-reactive N,N-dialkylated amino acid-based scaffold that is compatible with electron transfer dissociation (ETD). The ultimate goal of this aim is to determine how to most effectively combine the efficiencies of multiplexed quantification with the advantages of ETD for labile PTM identification.


Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison

Active date: 06/01/2021-05/31/2022

Emerging literature and personal evaluations demonstrate that trapped ion mobility spectrometry (TIMS) is the paradigm uniquely capable of expanding analytical sensitivity in proteomic, glycoproteomic, and small molecule analyses, while also presenting the highest gas-phase resolution regime for structural and conformational investigation. The innovative instrument design of the Bruker timsTOF fleX MS system incorporates several novel design improvements to the source area, TIMS cell, and quadrupole to dramatically enhance instrument performance.


“Combining microseparations and ion mobility mass spectrometry to probe peptidergic signaling in environmental stress”


Active date: 09/01/17-08/31/20

Brief description: The goal of this proposal is to develop novel ion mobility based MS platform and coupled to microseparations for enhanced peptidome coverage, improved isobaric quantitation of peptides involved in hypoxia stress conditions, D-amino acid containing peptide characterization and gas-phase ion isomer analysis for enhanced peptide identification.


Mass Spectrometric Studies of Neuropeptides in Feeding

Active date: 05/01/2006-05/31/2022

The outcome of the proposed research will be a suite of new analytical tools enabling quantitative assessment of the interplay of neuropeptides and biogenic amines with high spatial, chemical and temporal information. The parallel application of these new methods to both crustacean and mammalian nervous systems in feeding will accelerate our pace towards the development of new therapeutics for feeding disorders.


“In Situ Protein Characterization and Visualization in the Mammalian Brain”

(R56 MH110215-01A1)

Active date: 01/01/2017-12/31/2019

Brief description: The main goals of this project are to create next generation of MALDI orbitrap-based mass spectrometry imaging (MSI) technology that enables simultaneous mapping and quantifying in situ protein expression patterns in biological tissues from animal models of diseases and apply this novel platform to autism research.


Probing Protein Structural Changes in Alzheimers Disease

Active date: 01/15/2020-12/31/2022

Collectively, our proposed experiments will be the first system-wide, large-scale analysis of protein structure changes in AD. The newly discovered and validated conformational biomarkers would be invaluable in exploring molecular mechanism and designing therapeutic targets in Alzheimer’s disease.


A novel multi-faceted method for large-scale characterization and relative quantitation of citrullinated proteins for biological samples and its application to Alzheimer's disease

Active date: 08/15/2018-04/30/2022

Collectively, our proposed experiments will develop a novel MS-based method enabling large-scale and relative quantitation of citrullinated proteins in complicated biological samples. This is also the first time that the roles of citrullination in AD will be studied, advancing our knowledge of AD and providing an opportunity for new AD biomarker discovery.


Di-Leu-enabled multiplexed quantitation for biomarker discovery and validation in Alzheimer's disease

Active date: 01/15/2018-12/31/2022

This multifaceted approach will enable identification of biomarkers of AD in CSF that offer improved sensitivity and specificity for diagnosis and predict dementia onset and progression. These biomarkers would be invaluable in designing therapeutics for patient care and more efficient clinical trials of disease modifying therapies. The advances in technology and new insights will have broad impact on translational medicine.


“Defining a Proteomic Signature for Soy-Induced Metabolic Changes in Mice.”

Active date: 7/15/2018-7/14/2023

Brief description: Our goal is to identify nutritional biomarkers of soy consumption. Successful outcomes from these studies will identify altered metabolic phenotypes and define a proteomic signature in mice in response to soy consumption.

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