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Intramural Research Program (IRP)
Contents
Introduction
The mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is to improve health by leading the development of biomedical technologies and accelerating their application. The NIBIB encourages the integration of the physical sciences and the life sciences to advance human health by improving quality of life and reducing the burden of disease.
The NIBIB's Intramural Research Program (IRP), based in Bethesda, Maryland, has expertise that spans technologies ranging in scale from near atomic resolution to intact organisms.
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Current Research
- Biophotonics – Developing probes and techniques for use in diffraction limited and sub-diffraction limited fluorescence imaging of cells and tissues. Major emphasis is placed on developing new and improving existing genetically encoded fluorescent proteins for use as markers and sensors. Methods and technologies include confocal, TIRF, and widefield microscopies, single molecule imaging, fluorescence spectroscopy and protein engineering.
- Cardiovascular Imaging – Developing patient-based methods for detection and quantitative characterization of subclinical cardiovascular disease of the myocardium and blood vessels in both early phase clinical trials as well as in multi-center studies. Areas of study include genetically determined disease, as well as acquired cardiovascular disease as a result of common risk factors. Methods include advanced magnetic resonance techniques, cardiovascular computed tomography, and molecular probes.
- Complex Biological Systems – Developing novel instrumentation and mathematical models for improved understanding of complex biological systems at the nanoscale. Methods include high-resolution atomic force microscopy under physiological conditions with sensitive force measurments and mathematical modeling, optical and laser technologies, fluorescence and optical spectroscopy, and applications of novel reporter molecules.
- Dynamics of Macromoecular Assembly – Developing biophysical methods to characterize macromolecules and their reversible interactions, including elucidating the relationship between protein structure and function, and the assembly of multi-protein complexes and molecular machines. Methods include analytical ultracentrifugation, surface plasmon resonance biosensing, photon correlation spectroscopy, isothermal titration and differential scanning microcalorimetry, and circular dichroism.
- High Resolution Optical Imaging – Developing super-resolution optical imaging techniques, such as photoactivated localization microscopy, and applying them to the study of cells and tissues by combining wide-field optical sectioning techniques with existing approaches that utilize defocus or astigmatism for enhanced axial resolution. Developing fast optical sectioning techniques, such as selective plane illumination microscopy and multiphoton temporal focusing, that enable high-speed volumetirc imaging of cells and embyros.
- Immunochemcial Nanoscale Analysis and Diagnostics – Developing new technologies, including real-time, minimally-invasive, micro-dialysis techniques and "lab-on-a-chip" microfluidic immunoassays for the identification of biomolecules. Methods include microfabrication, laser induced fluorescence detection, measurement of analytes and sub-femtogram levels, mass spectrometry, time-resolved fluorescence, chromatographic analysis of protein expression and secretion from single cells.
- Molecular Imaging Probe Development – Developing molecular imaging probes for in vivo imaging of biochemical processes, including: positron emission tomography, optical imaging (fluorescence and Raman), magnetic resonance imaging, contrast enhanced ultrasound, photoacoustic and multimodal imaging. Molecular imaging in combination with anatomic and functional imaging can improve understanding of disease, enable early detection, and enhance monitoring of therapeutic responses and drug discovery and development. Methods include chemical systhesis, protein engineering, bioconjugation, radiolabeling, chemical analysis, preclinical studies, and clinical translation using various in vitro and in vivo techniques.
- Nano Theranostics – Rational design of water-soluble, biocompatible nanoparticles for combined imaging and therapy. Nanoparticles (<100nm) synthesized from materials such as polymers, metals, ceramics, and lipids permit simultaneous diagnostic imaging, drug delivery, and monitoring of therapeutic responses. Methods include synthesis, physiochemical characterization, surface modification and bioconjugation, pharmacokinetic, and pharmacodynamic evaluation in rodents for translation to clinical application.
- Non-Invasive Optical Imaging – Developing real-time, non-invasive methods to evaluate and monitor tissues and organs, with applications to cancer diagnosis and monitoring the viability of kidneys destined for transplantation. Methods include optical subsurface imaging of fluorophores, as well as senstive infrared imaging of thermal gradients in tissues.
- Pharmacokinetics and Drug Delivery – Modeling and improving delivery of drugs, including macromolecules, to targeted tissues in both animals and humans; and modeling the anatomical distribution of endogenous metabolites and environmental contaminants. Methods include estimation of dose response, toxicity, diffusion, fluid flow, convection, and interactions with cellular receptors.
- Supramolecular Structure and Function – Determing the organization and composition of supramolecular assemblies and small organelles in a cellular context, and relating structure to function at the subcellular and molecular level. Methods include quantitative, high-resolution electron microscopy, scanning transmission electron microscopy, electron tomography, electron spectroscopy, nanoscale spectroscopic imaging, and novel labeling techniques.
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Training Opportunities
The NIBIB's IRP offers training opportunities at several educational levels.
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NIBIB Contact
Dr. Richard Leapman
Scientific Director
Intramural Research Program
Telephone: 301-496-2599
leapmanr@mail.nih.gov
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