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Cellular Biophysics is the application and development of biophysical methods for the exploration of molecular processes in single cells, tissues, and animals. Their relevance to disease is an exciting field, developed in our Program, and reflecting the long standing commitment to and internationally recognized expertise in biophysics at the The application of biophysical approaches to address the mechanisms of biological processes occurs at every level and across many fields from the theoretical to the experimental, and multi-disciplinary training experience is offered to students with backgrounds in the Biological, Chemical, Physical, and Mathematical Sciences. Students in this Program, although from varied backgrounds, share a common intellectual goal of understanding the physical and chemical basis of complex biological processes and this perspective sets them apart from cell and molecular biologists. Research Areas: Several laboratories use advnaced light microscopy imaging approaches. Dr. Michael Lawrence uses high speed video microscopy (600 frames/sec) in controlled force assays to quantitatively describe receptor mediated cell adhesive phenomena, such as signaling by highly specialized receptors that direct movement of leucocytes from the circulation to specific cites of tissue injury and infection where the duration and strength of adhesive interactions between leucocytes and the vascular endothelium are measured. The development of electron energy loss spectroscopy and X-ray microprobe analysis, in conjunction with rapid freeze trapping of biological processes on a millsec time base, is used to map the elemental composition at nanometer spatial resolution to measure the transport of elements such as Ca across cellular organelles. Dr. Avril V. Somlyo , in whose laboratory these technologies have been developed, uses them to determine the role of the high concentration of calcium localized in compositional maps with (10nm pixel resolution) to the intercalated discs of cardiac muscle. This localization is consistent with the location of cadherins, molecules that calcium dependently mediate cell adhesion between adjacent cardiac myocytes. Dr. David Castle studies the molecular mechanisms of protein sorting and cell secretion and uses such technologies as carbon fiber amperometry , in collaboration with Dr. Gabor Szabo , to study single exocytotic events to determine the role of specific members of the SNARE protein family that regulate membrane fusion at the cell surface. Dr. William Guilford determines the properties of molecular motors, using an in vitromotility assay and laser trap transducer for single cells and small translucent particles trapped and held in 3-dimensional space. These methods allow measurements of elasticity, distance moved and force generated by a single protein molecules and by motor proteins such as myosin involved in contraction and cell movement and the strength of single adhesion receptor bonds. In addition to approaches using biochemistry, molecular biology and genetics, Dr. Carl Creutz uses fluorescent resonant energy transfer techniques to monitor membrane protein interactions, such as membrane fusion and protein self-assembly on membrane surfaces. These fundamental studies on the mechanisms of exocytosis may provide a basis for understanding the action of drugs that affect hormone or neurotransmitter release, and may also lead to development of new pharmacological agents that influences these processes. The Somlyo laboratory uses laser flash photolysis of caged compounds to avoid diffusional delays and to measure the kinetics of the signaling pathways that lead to contraction and relaxation of smooth muscle, as well as caged and fluorescently labeled nucleotides for kinetic studies of the myosin motors and their regulation of fast smooth muscles of the gut comparing them with the slow tonic type smooth muscle of large blood vessels. Dr. Thomas Skalak central research thrust is directed to the understanding of vascular adaptation to environmental conditions in disease using 3-dimensional reconstruction of vascular networks, intravital microscopy measurements of blood flow and pressure, vessel dimensions and vascular reactivity, gene expression profiling, integrated device design and prototyping for fluid transport in skin flaps and skin ulcer studies, continuum mechanical studies of network hemodynamics and discrete cell-based computer simulation of vascular adaptation.
The above descriptions provide a glimpse of some of the types of projects in which students could participate and learn to apply state of the art biophysical approaches to advance our understanding of significant biological problems that relate to human disease. For more specific information, visit the investigators’ respective websites. Technologies and instrumentation available:
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