Mass spectrometry is an extraordinarily powerful bioanalytical technique that has had a profound impact on our molecular understanding of human health and disease. Major advances in mass analyzer technology, 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 to be made allowing an even more diverse array of biological questions to be addressed. This proposal is centered on the development of new ionization methods for biological mass spectrometry to allow for tissue imaging with top-down characterization. The short-term objective of this proposal is to develop and understand these new ionization methods using chemical and molecular systems. These results will provide a solid foundation from which biological applications will directly benefit. In this mindset, we will develop and apply these new ionization methods to tissue imaging. The long- term objective is to establish these new ionization methods as an enabling bioanalytical technology to effectively address questions in human health and disease. 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. A prerequisite of MS is to convert neutral molecules into charged species (ions) such that they can be "weighed" by the mass spectrometer. The focus of this research is to develop new ionization methods allowing a more diverse array of contemporary biomedical questions to be addressed. This will include the imaging of tissues to ultimately provide diagnostic and prognostic biomarkers.

Public Health Relevance

This proposal seeks support to develop new ionization methods for biological mass spectrometry that will enable tissue imaging with identification via top-down methods. Furthermore, these ionization methods will be broadly applicable to the fields of proteomics and systems biology. In summary, we will establish a new enabling bioanalytical technology through detailed characterization using model molecular and chemical systems and demonstrate its application to tissue imaging.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM087964-03
Application #
8309280
Study Section
Enabling Bioanalytical and Biophysical Technologies Study Section (EBT)
Program Officer
Edmonds, Charles G
Project Start
2010-09-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$303,097
Indirect Cost
$63,961
Name
North Carolina State University Raleigh
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Nazari, Milad; Muddiman, David C (2016) Enhanced Lipidome Coverage in Shotgun Analyses by using Gas-Phase Fractionation. J Am Soc Mass Spectrom 27:1735-1744
Rosen, Elias P; Thompson, Corbin G; Bokhart, Mark T et al. (2016) Analysis of Antiretrovirals in Single Hair Strands for Evaluation of Drug Adherence with Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging. Anal Chem 88:1336-44
Nazari, Milad; Muddiman, David C (2016) Polarity switching mass spectrometry imaging of healthy and cancerous hen ovarian tissue sections by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI). Analyst 141:595-605
Loziuk, Philip; Meier, Florian; Johnson, Caroline et al. (2016) TransOmic analysis of forebrain sections in Sp2 conditional knockout embryonic mice using IR-MALDESI imaging of lipids and LC-MS/MS label-free proteomics. Anal Bioanal Chem 408:3453-74
Bokhart, M T; Muddiman, D C (2016) Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging analysis of biospecimens. Analyst 141:5236-45
Nazari, Milad; Bokhart, Mark T; Muddiman, David C (2016) Whole-body Mass Spectrometry Imaging by Infrared Matrix-assisted Laser Desorption Electrospray Ionization (IR-MALDESI). J Vis Exp :e53942
Bokhart, Mark T; Rosen, Elias; Thompson, Corbin et al. (2015) Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization. Anal Bioanal Chem 407:2073-84
Thompson, Corbin G; Bokhart, Mark T; Sykes, Craig et al. (2015) Mass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirs. Antimicrob Agents Chemother 59:2944-8
Nepomuceno, Angelito I; Muddiman, David C; Petitte, James N (2015) Global Proteomic Analysis of Functional Compartments in Immature Avian Follicles Using Laser Microdissection Coupled to LC-MS/MS. J Proteome Res 14:3912-23
Nazari, Milad; Muddiman, David C (2015) Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling. Anal Bioanal Chem 407:2265-71

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