Research Overview My research involves the application of Multinuclear Magnetic Resonance spectroscopy and imaging to problems in biology and medicine. The projects range from NMR spectroscopic studies of the nitrogen and phosphorus metabolism of cyanobacteria (in collaboration with Mary M. Allen of the Department of Biological Sciences and Adele J. Wolfson of the Department of Chemistry), to the study of neural development in mice and crustaceans using micro-MRI (in collaboration with Susan J. Kohler of the Science Center and Barbara Beltz and Joanne Berger-Sweeney of the Department of Biological Sciences). In the past, my medical work was in the field of ophthalmology and focused on eye diseases such as uveal melanoma and diabetic retinopathy, and on the physiology of aqueous humor production. NMR spectroscopy and imaging are extremely sensitive to the physical environment of nuclei such as protons, nitrogen, sodium or phosphorus. NMR spectroscopy enables us to study the structures of complex biological molecules in solution, the synthesis and distribution of polypeptides, or the phosphate metabolism of living systems. MRI is based on the behavior of water protons or sodium ions in animals or humans and enables us to perform static or dynamic studies of these organisms. All magnetic resonance studies are carried out at the NMR/micro-NMR Facility at Wellesley College. Over the years my research students have been equal partners in my projects. Students have been co-authors on many of my publications and have presented their work at local, national and international scientific meetings. The type of project in which a student becomes involved depends upon her interests, but there are opportunities in every area described on this website.

Student Research Projects NMR Spectroscopic Studies of the Nitrogen Metabolism of Cyanobacteria I am part of an interdisciplinary team of faculty (Mary M. Allen, Nancy H. Kolodny and Adele Wolfson) and students in chemistry, biological chemistry and biology who are investigating the synthesis and degradation of two nitrogen storage molecules in cyanobacteria. One of them is cyanophycin (multi-L-arginyl poly-[L-aspartic acid], the only known non-protein polymer whose function is the storage of nitrogen, and the other is phycocyanin, a protein involved in light harvesting. We study the metabolism of these molecules by enzyme analysis and purification, and by in vivo and in vitro NMR spectroscopy after labeling cyanobacteria with 15N-labeled nitrogen sources. Nitrogen metabolism is investigated during normal growth and during growth under various conditions of nutrient stress, including nitrogen starvation, light limitation, and blocking of ribosomal protein synthesis with chloramphenicol. Experiments have been designed to determine whether cyanophycin and phycocyanin have a dynamic role in cyanobacterial metabolism. Our 1H NMR spectroscopic experiments on cyanophycin and phycocyanobilin isolated from small volumes of cyanobacteria enable us to determine both the amount of cyanophycin produced and the relative extent of 14N and 15N labeling of cyanophycin or phycyanobilin. This technique has been used successfully by students to study cyanobacteria grown under a variety of stressful conditions. In addition, gel electrophoresis of the cell samples has indicated the production of at least one unique protein at levels varying with time under stress. Each of these techniques holds great promise for projects that study a wide range of wild type and mutant cyanobacteria under conditions of environmental stress. MRI Studies in Neuroscience Interdisciplinary research opportunities in Magnetic Resonance Imaging (MRI) are now open to students at Wellesley. Thanks to a grant from the National Science Foundation we have established a Magnetic Resonance Micro-Imaging Facility in Wellesley's Science Center. With the establishment of the micro-imaging facility, several projects are underway using proton MRI and in vivo NMR spectroscopy (MRS) at 9.4 T. These techniques are being used to answer important neurobiological questions. MRI studies are being conducted to examine the brains of crustaceans such as crayfish, and mice. Neural activity in the olfactory and visual pathways of the crustacean brain will be studied using manganese-enhanced MRI. We also are developing a serotonin-responsive contrast agent that will be used to examine questions related to the role of serotonin, an important brain biochemical, in olfactory neurons in newborn crustaceans. In mice, both MRI and MRS techniques are being implemented to study brain development in a mouse model for Rett Syndrome, a neurodevelopmental disorder of girls.

Research Presentations

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Susan D. Kunk  Nancy H. Kolodny  September 8, 2004  August 25, 2006