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.
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.
| Adams, Kendra J; Smith, Natalie F; Ramirez, Cesar E et al. (2018) Discovery and targeted monitoring of polychlorinated biphenyl metabolites in blood plasma using LC-TIMS-TOF MS. Int J Mass Spectrom 427:133-140 |
| Garabedian, Alyssa; Benigni, Paolo; Ramirez, Cesar E et al. (2018) Towards Discovery and Targeted Peptide Biomarker Detection Using nanoESI-TIMS-TOF MS. J Am Soc Mass Spectrom 29:817-826 |
| Benigni, Paolo; Marin, Rebecca; Sandoval, Kathia et al. (2017) Chemical Analysis of Water-accommodated Fractions of Crude Oil Spills Using TIMS-FT-ICR MS. J Vis Exp : |
| Jeanne Dit Fouque, Kevin; Garabedian, Alyssa; Porter, Jacob et al. (2017) Fast and Effective Ion Mobility-Mass Spectrometry Separation of d-Amino-Acid-Containing Peptides. Anal Chem 89:11787-11794 |
| Benigni, Paolo; Sandoval, Kathia; Thompson, Christopher J et al. (2017) Analysis of Photoirradiated Water Accommodated Fractions of Crude Oils Using Tandem TIMS and FT-ICR MS. Environ Sci Technol 51:5978-5988 |
| Molano-Arevalo, Juan Camilo; Jeanne Dit Fouque, Kevin; Pham, Khoa et al. (2017) Characterization of Intramolecular Interactions of Cytochrome c Using Hydrogen-Deuterium Exchange-Trapped Ion Mobility Spectrometry-Mass Spectrometry and Molecular Dynamics. Anal Chem 89:8757-8765 |
| 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 |
| 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 |
| Garabedian, Alyssa; Butcher, David; Lippens, Jennifer L et al. (2016) Structures of the kinetically trapped i-motif DNA intermediates. Phys Chem Chem Phys 18:26691-26702 |
| Ramirez, Cesar E; Nouzova, Marcela; Benigni, Paolo et al. (2016) Fast, ultra-trace detection of juvenile hormone III from mosquitoes using mass spectrometry. Talanta 159:371-8 |
Showing the most recent 10 out of 32 publications
