Laboratory of Integrative and Medical Biophysics

LABORATORY OF INTEGRATIVE AND MEDICAL BIOPHYSICS

Ralph Nossal, PhD, Chief

The Laboratory of Integrative and Medical Biophysics (LIMB) performs cross-disciplinary research leading to deeper understanding of cell and tissue processes in both normal and disease states. It also develops new methodologies for biomedical research and diagnosis. The LIMB’s work links biomedical research with experimental and theoretical techniques commonly associated with research in the physical and engineering sciences. Specialized interests and expertise extend to optical imaging of biological tissues, magnetic resonance imaging, mathematical modeling, methods of quantitative cell biology, techniques for assessing ultra-small biological samples, and polymer physics and physical chemistry. The laboratory’s capabilities include advanced physical methods such as diffuse optical tomography, magnetic resonance imaging, neutron scattering, fluorescence correlation spectroscopy, and an ability to formulate mathematical and computational models. Investigators study biological function at levels of complexity varying from molecule to tissue, focusing on interactive behavior at different length and time scales. Much of the LIMB’s work is strongly collaborative, and a number of research projects are carried out with colleagues in other NIH branches and laboratories as well as with investigators at other institutions.

Peter Basser heads the Section on Tissue Biophysics and Biomimetics, which seeks to understand fundamental relationships between function and structure in soft tissues, in “engineered” tissue constructs and in tissue analogs (e.g., polymer gels). In combination with descriptive biological analysis, members of the section develop new physical theories, mathematical and computational models, and biomimetic tissue analogs to aid in the design and interpretation of biological experiments. The section also continues its development of Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) as a probe of tissue structure in normal or diseased organs, with particular emphasis on developing quantitative methods for improving resolution and specificity in applications involving brain and other soft tissues.

Led by Robert Bonner, the Section on Medical Biophysics focuses on interdisciplinary translational research and new enabling technologies, which are founded on its success in developing and evaluating new optical technologies for clinical research, diagnosis, and treatment. The section continues its work in advancing technologies for isolating targeted cells for use in genomic and proteomic investigation of tissue pathology and in studies of developing organisms. Current emphasis is on developing an automated, laser-based microtransfer method that employs cell-specific stains and that can be used for proteomics and lipid-based studies. In addition, the section is investigating the role of chronic phototoxicity in the outer retina as a driving force for age-related macular degeneration (AMD), with the goal of developing a biophysical model to predict photochemical changes in the eyes of an aging population and of developing optical filters to arrest disease progression.

Amir Gandjbakhche’s Section on Biomedical Stochastic Physics works primarily on noninvasive optical imaging of biological tissues. The section is carrying out a multifaceted experimental and computational research program that incorporates mathematical and physical theories and technologies, experimental models, and collaborative clinical investigations. Current projects include time-resolved illumination of thick tissue for quantitative spectroscopy of tumors, the use of specific fluorescent markers for identifying disease processes, fluorescence-lifetime functional imaging, near-infrared and visible light multispectral imaging, and multimodality imaging combining thermography and laser-Doppler bloodflowmetry. The section also has initiated a project to study aspects of tumor-induced angiogenesis by using mathematical modeling and observations of tissue culture cells to understand the proliferation and patterning of endothelial cells recruited from existing blood vessels.

Ralph Nossal’s group, the Section on Cell Biophysics, aims to understand the physical basis for various cell activities that involve structural changes in supramolecular biomolecular complexes. The long-term goal is to build and use an arsenal of tools, both theoretical and experimental, to study kinetic aspects of cell processes and to increase knowledge of ways those activities can be mediated by external interventions. The section’s activities include the use of fluorescence correlation spectroscopy (FCS) to study the structure and stability of supramolecular biological assemblies, the development of FCS and total internal reflectance microscopy (TIRFM) to study events occurring on or near the plasma membranes of live cells, and the creation of mathematical models to obtain estimates of energies relating to the formation of vesicles involved in intracellular trafficking. The section also carries out a variety of projects on tubulin polymers, with emphasis on drug-tubulin interactions and the ways that environmental factors affect formation of tubulin polymers.