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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Career Transition Award (K99)
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Special Emphasis Panel (ZGM1-BRT-9 (KR))
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Sheeley, Douglas
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Texas A&M University
Schools of Arts and Sciences
College Station
United States
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Debord, J D; Fernandez-Lima, F A; Verkhoturov, S V et al. (2013) Characteristics of positive and negative secondary ions emitted from [Formula: see text] and [Formula: see text] impacts. Surf Interface Anal 45:134-137
Eller, M J; Verkhoturov, S V; Fernandez-Lima, F A et al. (2013) Simultaneous detection and localization of secondary ions and electrons from single large cluster impacts. Surf Interface Anal 45:
Fernandez-Lima, F A; Debord, J D; Schweikert, E A et al. (2013) Surface characterization of biological nanodomains using NP-ToF-SIMS. Surf Interface Anal 45:
Fernandez-Lima, Francisco A; Henkes, Aline VerĂ´nica; da Silveira, Enio F et al. (2012) Alkali Halide Nanotubes: Structure and Stability. J Phys Chem C Nanomater Interfaces 116:
Debord, J Daniel; Della-Negra, Serge; Fernandez-Lima, Francisco A et al. (2012) Bi-Directional Ion Emission from Massive Gold Cluster Impacts on Nanometric Carbon Foils. J Phys Chem C Nanomater Interfaces 116:8138-8144
Fernandez-Lima, Francisco Alberto; Nascimento, Marco Antonio Chaer; da Silveira, Enio Frota (2012) Alkali halide clusters produced by fast ion impact. Nucl Instrum Methods Phys Res B 273:102-104
Fernandez-Lima, F A; Eller, M J; Debord, J D et al. (2012) On the Surface Mapping using Individual Cluster Impacts. Nucl Instrum Methods Phys Res B 273:270-273
Fernandez-Lima, Francisco A; Eller, Michael J; Debord, J Daniel et al. (2012) Analysis of Fluorescent Proteins with a Nanoparticle Probe. J Phys Chem Lett 3:337-341
Fernandez-Lima, F A; Kaplan, D A; Park, M A (2011) Note: Integration of trapped ion mobility spectrometry with mass spectrometry. Rev Sci Instrum 82:126106
Fernandez-Lima, Francisco; Kaplan, Desmond A; Suetering, J et al. (2011) Gas-phase separation using a trapped ion mobility spectrometer. Int J Ion Mobil Spectrom 14:

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