Susan R. Wente, Ph.D., associate professor of cell biology and physiology, has received two grants totaling $2 million from the National Institute of General Medical Sciences.
A four-year $1.2 million grant will allow her to continue studying how cells export material from the nucleus. With a four-year $798,867 grant, Wente will examine the formation of nuclear pores where this transport occurs.
"We want to understand how cells exchange information between their two main compartments: the nucleus where genetic material is stored and the cytoplasm where many cellular activities are carried out," Wente said. The findings could have implications for treating viral infections, cancer and other diseases that require movement of factors between the two compartments.
Cellular cargo is shuttled to and from the nucleus through holes in its membrane that are surrounded by a large protein complex called the nuclear portal or nuclear pore complex. Wente will study how nuclear export occurs by analyzing three proteins important for transport in everything from yeasts to human cells.
She will study budding yeast called Saccharomyces cerevisiae to investigate the interactions of Kap95p, a nuclear import factor, with two pore proteins as it recycles to the cytoplasm. Previous work in her laboratory has shown that Kap95p binds a repeated sequence within the two pore proteins. Wente will analyze this interaction using mutated versions of the pore proteins and determine whether other transport factors bind similar repeats.
In the second grant, Wente will study the initial formation of nuclear pores and the location of proteins within the final structure. She will generate yeast containing abnormal pores to determine how their underlying protein problems alter the rate of pore formation or their ability to transport material. To visualize the abnormalities, she will use yeast that contain one of several pore proteins with a fluorescent green protein attached. The fluorescence broadcasts the location of individual pore complexes so that cells with fewer pores, unusual clusters of pores or other abnormalities can be visually identified. Wente already is analyzing one mutant pore protein identified in this manner that results in portals with an altered outer opening.
The information gained on the nuclear pores of yeast cells will allow her to search for proteins with similar functions in vertebrate cells. "Our long-range holy grail is to determine what triggers the initial pore formation," Wente said.
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