Our main objective is to understand the molecular mechanisms by which normally soluble proteins undergo transformations that lead to disease. For many years we have been trying to determine the mechanisms by which genetic mutations and chemical modifications of the crystallin proteins in the eye lens, lead to a variety of genetic and age-onset cataracts respectively. In the last 5 years, based on available genetic and epidemiological data, we examined the mutant proteins involved and proposed molecular mechanisms connecting the observed pathology (or phenotype) with altered molecular interactions of the proteins as a result of mutation.

We examine the proteins by expressing native and mutant crystallins in E. coli and comparing their physico-chemical properties. Our in-vitro studies have resulted in some novel findings: We have shown that unlike the native proteins which are highly soluble, the mutant proteins undergo a variety of phase transformations. As a result, various condensed-phases appear readily in aqueous solutions of these crystallin mutants. These protein condensed-phases are responsible for the light scattering and opacity that leads to cataract. Despite these significant phase changes however, the 3-D structure (x-ray) of the mutant proteins remains largely intact. We intend to expand these studies and use high-resolution protein-structure determination techniques in solution to determine if minor and specific structural perturbations occur in the solution state that lead to protein condensation. For the high-resolution protein structure determination, the university has recently acquired a 700 MHz NMR spectrometer. We will continue to work with our collaborators to determine the x-ray crystal structure, of other native and mutant proteins.

The next phase of our work will be expanded to studies of intact normal and cataractous lens cells, to determine if protein-condensation does indeed occur in these cells and lead to light scattering and opacity. We will examine lens epithelial and fiber cells using optical imaging and micro-spectrophotometry. We are in the process of purchasing a Raman microscope.

Besides the lens, protein condensation due to aging and genetic changes is known to cause disease in many other organs of the body. We and others have hypothesized that condensation of mutant myocilin proteins is responsible for some forms of glaucoma. We have done preliminary studies on myocilin-linked glaucoma and have applied for a pilot-project grant from NIH for this purpose.

In summary, our focus will continue to be on the structural and functional changes in proteins that cause diseases such as cataract and glaucoma. In addition, we will also form a subgroup dedicated to imaging of cells and tissue sections in healthy and diseased cells, using Infra-red and Raman microscopic techniques.

UAlbany, is a part of the State University of New York system, and is located in the state capital, Albany . The city itself is a vibrant center for multi-cultural events and entertainment. It is within an hour of Saratoga Spring (with the well known Saratoga Performing Arts Center ), the Berkshires (where the Tanglewood music festival is held), the Catskills, and the Adirondack Mountains . All are areas famed for recreational and cultural opportunities. The University is located 150 miles from New York City , 165 miles from Boston , and 242 miles from Montreal . The main campus is located near the intersection of the New York State Thruway, the Adirondack Northway, and Interstate 90. Within five miles of the campus are an AMTRAK rail station, the Greyhound and Trailways bus depots, and Albany International Airport , served by several major airlines.