NMR studies of allosteric proteins
The research goal in this laboratory is to understand the relationships between structure and function in biological systems by correlating information obtained from biochemical, biophysical, and molecular biological techniques. Two major research projects are currently under way.
The first research area centers on a study of human normal and mutant hemoglobins in order to understand the molecular mechanism of transport of oxygen from the lungs to the tissues. We have constructed an expression plasmid to produce authentic human normal adult hemoglobin in Escherichia coli. With this expression system, we can design and express any mutant hemoglobins needed for our research on the structure-function relationship in hemoglobin. Some of our designed recombinant hemoglobins are potential candidates for hemoglobin-based oxygen carriers and/or hemoglobin therapeutics. Our hemoglobin research is an excellent illustration of the power of combining information obtained from x-ray crystallography, NMR spectroscopy, computer modeling, molecular genetics, and functional studies to correlate the structure-function relationship of an allosteric protein under physiological conditions at atomic resolution.
The second research area centers on the application of NMR to living systems, both by imaging (MRI); and by spectroscopic (MRS); methods. Currently, we are developing techniques to monitor the migration of immune cells in vivo by magnetic MRI using dextran-coated superparamagnetic iron oxide particles as contrast agents. This work may offer a new non-invasive approach to detecting early signs of organ rejection after transplantation. Our approach can readily be adapted to track cell movement of other cell types, provided that an MRI contrast agent can be non-invasivelyincorporated into the cells and that there is sufficient sensitivity for MRI detection.
Massachusetts Institute of Technology
Carnegie Mellon University
Department of Biological Sciences
649 Mellon Institute
4400 Fifth Avenue
Pittsburgh, PA 15213
Phone: (412) 268-3395
Fax: (412) 268-7129