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Principal Investigator: Martina Ralle
Organization: OREGON HEALTH & SCIENCE UNIVERSITY
Fiscal Year: 2019
Award: $254,898
Funding agency: National Institute of General Medical Sciences
Project Summary
X-ray fluorescence microscopy (XFM) has emerged as powerful tool to visualize metals within cells or tissue.
Using X-ray microprobes, investigators can now produce elemental maps of biological material at the cellular
and subcellular levels. Determining the elemental distribution and concentration at such resolution, however, is
of little use without the option to also identify subcellular compartments or localizing key proteins with which the
element in question is associated. To date, without additional, correlative techniques, it is impossible to do so
unless the organelle in question shows an increased concentration in one of the detected elements (e.g.
phosphorus to identify the nucleus). This proposal seeks to develop a novel robust technique in which
elemental imaging and organelle localization is done simultaneously, as part of the regular XFM scan and at
energies ≤10 keV. In Specific Aim1 we will synthesize nanoparticle containing probes that are tethered to
antibodies via click chemistry. The nanoparticles will either contain Ni and/or Co as the central metal and the
antibodies will be against organelle markers such as Lamp1 for lysosomes. Using XFM we will then be able to
visualize the organelles, albeit indirectly, through their Ni (or Co) signature and the element of interest in one
scan. The application of Specific Aim1 is limited to chemically fixed samples. In other experiments, direct, in
vivo labeling might be desired to avoid elemental redistribution due to chemical fixation and permeabilization
processes. This is especially important when the elements of interests are only loosely bound. In Specific Aim
2 we will therefore design and synthesize hybrid lipid-coated nickel nanoparticles of which the surface
architecture will be tuned to target specific organelles.
Terms: <Adrenal Glands><Adrenals><Alzheimer><Alzheimer Type Dementia><Alzheimer disease><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Disease><Alzheimers Dementia><Alzheimers disease><Antibodies><Architecture><Area><Autoregulation><Azides><Biocompatible Materials><Biological><Biomaterials><Body Tissues><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Components><Cell Nucleus><Cell Signaling><Cell Structure><Cells><Cellular Structures><Cellular biology><Cerebral Pseudosclerosis><Chemicals><Chemistry><Congenital Hypocupremia><DNA Molecular Biology><Degenerative Neurologic Diseases><Degenerative Neurologic Disorders><Development><Effectiveness><Electron Microscopy><Elements><Encephalon><Endocytosis><Endoplasmic Reticulum><Engineering><Engineering / Architecture><Enzyme Gene><Enzymes><Ergastoplasm><Exhibits><Fixation><Fluorescence Light Microscopy><Fluorescence Microscopy><Gowers' chorea><Hepato-Neurologic Wilson Disease><Hepatocerebral Degeneration><Hepatolenticular Degeneration><Homeostasis><Hybrids><Image><In Vitro><Intracellular Communication and Signaling><Intracellular Structure><Investigators><Kinky Hair Disease><Kinky Hair Syndrome><Kinnier-Wilson Disease><Label><Lipids><Location><Lysosomes><Maleimides><Maps><Menkes Kinky Hair Syndrome><Menkes Syndrome><Menkes disease><Metals><Methodology><Molecular Biology><Nervous System Degenerative Diseases><Neural Degenerative Diseases><Neural degenerative Disorders><Neurodegenerative Diseases><Neurodegenerative Disorders><Neurohepatic Degeneration><Neurologic Degenerative Conditions><Ni element><Nickel><Noise><Nucleus><Organelles><P element><Pancreas><Pancreatic><Pathogenesis><Phosphorous><Phosphorus><Physiological Homeostasis><Population><Primary Senile Degenerative Dementia><Process><Progressive Lenticular Degeneration><Proteins><Pseudosclerosis><Research><Research Personnel><Research Specimen><Researchers><Resolution><Respiration><Roentgen Rays><Sampling><Scanning><Signal Transduction><Signal Transduction Systems><Signaling><Source><Specimen><Steely Hair Disease><Steely Hair Syndrome><Subcellular structure><Surface><Synchrotrons><Syndrome><System><Techniques><Temperature><Tennessee><Testing><Time><Tissues><Universities><Westphal Strumpell disease><Westphal pseudosclerosis><Westphal-Strumpell Syndrome><Wilson Disease><Wound Healing><Wound Repair><X-Radiation><X-Rays><X-Rays Radiation><X-linked copper malabsorption><Xrays><absorption><aqueous><base><beamline><biological material><biological signal transduction><cell biology><chemical fixation><congenital hypocupraemia syndrome><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><dementia of the Alzheimer type><design><designing><developmental><experiment><experimental research><experimental study><familial hepatitis><fascinate><imaging><in vivo><interest><microscope imaging><microscopic imaging><microscopy imaging><nano particle><nano probe><nano-sized particle><nanoparticle><nanoprobe><nanosized particle><neurodegenerative illness><new marker><novel><novel biomarker><novel marker><primary degenerative dementia><protein complex><respiratory mechanism><sample fixation><senile dementia of the Alzheimer type><suprarenal gland><tool><trans-Golgi Network><trichopoliodystrophy>