Title: "Mass Spectrometry based imaging of native biological nanodomains" 6. PROJECT SUMMARY/ABSTRACT The application proposes a career development for Dr. Francisco A. Fernandez-Lima, a postdoctoral fellow trained in biological mass spectrometry and instrument &method development. Dr. Fernandez- Lima is committed to a research career in biophysical science to study scientific problems at a molecular and cellular levels by creating new and improving current techniques and methods, that can be further translated to animal based studies, to patient-oriented clinical research, and ultimately lead to improved patient care. The applicant will be mentored by Dr. Emile A. Schweikert in nanometer scale imaging probes for mass spectrometry, co-mentored by Dr. David H. Russell in instrument and method development for biological mass spectrometry, and co-mentored by Dr. Jennifer L. Bizon in behavioral and cellular neuroscience methods and animal models for studies of cognitive impairment diseases. The project, to be conducted at Texas A&M University, proposes the instrumental development of a mass spectrometer coupled to a nanometer imaging probe capable of interrogating native biological surfaces at the single cell and sub-cellular levels (currently not available at the level proposed). The instrument (Specific Aim 1) will employ a cluster beam probe (Au100n+q and Binq+q) at up to 100 qkeV energies for enhanced molecular yield emission (~10 fold increase), and molecular ion localization with sub-100nm lateral resolution using an electron emission microscope. The methodology will be validated using well-defined cellular systems containing known surface markers (e.g., expression of CD4 antigen and hepatocyte growth factor receptor (c-met) from Immune cells (Molt-3) and hepatocytes) to characterize the instrument performance (Specific Aim 2). Fast gas-phase separation (in this case Ion Mobility - Mass Spectrometry, IM-MS) and fragmentation techniques (IM-CID-MS) will be applied to the separation and identification of molecular biomarkers (Specific Aim 3). As a short- term goal, the neuron phenotypic expression, morphology, and/or stability will be correlated with the basal forebrain chemical environment of behaviorally characterized young, middle-aged, and aged F344 rats (Specific Aim 4). Relevance: The project will set the instrumental and methodological basis for single cell and sub-cellular studies of molecular markers associated with cognitive impairment diseases by directly correlating the chemical environment with their biological function using untreated tissue samples.

Public Health Relevance

The biological performance at the cellular level is mediated by the chemical environment and surface chemistry. A new instrument and method will be created which can examine molecular composition on native biological surfaces. A unique feature will be the localization of biological markers with a resolution improved one hundred-fold over light microscopy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Transition Award (R00)
Project #
5R00GM106414-04
Application #
8528637
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sheeley, Douglas
Project Start
2010-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$238,134
Indirect Cost
$46,646
Name
Florida International University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
071298814
City
Miami
State
FL
Country
United States
Zip Code
33199
Benigni, Paolo; DeBord, J Daniel; Thompson, Christopher J et al. (2016) Increasing Polyaromatic Hydrocarbon (PAH) Molecular Coverage during Fossil Oil Analysis by Combining Gas Chromatography and Atmospheric-Pressure Laser Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR MS). Energy Fuels 30:196-203
Adams, Kendra J; DeBord, John Daniel; Fernandez-Lima, Francisco (2016) Lipid specific molecular ion emission as a function of the primary ion characteristics in TOF-SIMS. J Vac Sci Technol B Nanotechnol Microelectron 34:051804
Gonzalez, Walter G; Ramos, Victoria; Diaz, Maurizio et al. (2016) Characterization of the Photophysical, Thermodynamic, and Structural Properties of the Terbium(III)-DREAM Complex. Biochemistry 55:1873-86
Adams, Kendra J; Montero, Dennise; Aga, Diana et al. (2016) Isomer Separation of Polybrominated Diphenyl Ether Metabolites using nanoESI-TIMS-MS. Int J Ion Mobil Spectrom 19:69-76
Vanbellingen, Quentin P; Castellanos, Anthony; Rodriguez-Silva, Monica et al. (2016) Analysis of Chemotherapeutic Drug Delivery at the Single Cell Level Using 3D-MSI-TOF-SIMS. J Am Soc Mass Spectrom 27:2033-2040
Benigni, Paolo; Marin, Rebecca; Molano-Arevalo, Juan Camilo et al. (2016) Towards the Analysis of High Molecular Weight Proteins and Protein complexes using TIMS-MS. Int J Ion Mobil Spectrom 19:95-104
Schenk, Emily R; Almeida, Raybel; Miksovska, Jaroslava et al. (2015) Kinetic intermediates of holo- and apo-myoglobin studied using HDX-TIMS-MS and molecular dynamic simulations. J Am Soc Mass Spectrom 26:555-63
Schenk, Emily R; Nau, Frederic; Fernandez-Lima, Francisco (2015) Theoretical predictor for candidate structure assignment from IMS data of biomolecule-related conformational space. Int J Ion Mobil Spectrom 18:23-29
Benigni, Paolo; Thompson, Christopher J; Ridgeway, Mark E et al. (2015) Targeted high-resolution ion mobility separation coupled to ultrahigh-resolution mass spectrometry of endocrine disruptors in complex mixtures. Anal Chem 87:4321-5
McKenzie-Coe, Alan; DeBord, John Daniel; Ridgeway, Mark et al. (2015) Lifetimes and stabilities of familiar explosive molecular adduct complexes during ion mobility measurements. Analyst 140:5692-9

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