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Professor awarded $1.45 million NIH grant to analyze genetic interactions of cells

SYRACUSE, N.Y. — David Amberg, Ph.D., associate professor of biochemistry and molecular biology, has been awarded a 4-year, $1.45 million grant from the National Institutes of Health to systematically analyze and identify complex genetic interactions in cells. In this study, Amberg will use the cytoskeletal system of yeast to model the genetic interactions of complex systems. Research into genetic interactions in cells is considered vital to further understanding of human genetic disorders.

The NIH grant comes on the heels of a breakthrough in identifying binary gene interactions that Amberg and his research team report on in the Jan. 15 issue of Genes and Development. Amberg and his colleagues have developed a large-scale reverse genetic screen to identify complex haploinsufficient genetic interactions. Haploinsufficiency occurs when an individual inherits only one good copy of a gene as opposed to the normal two copies. A resulting lowering in the amount of gene product can lead to human disease. For example, haploinsufficiency of “tumor suppressor” genes has been implicated in the development of certain cancers. The advance reported in this new study from the Amberg lab is to measure the effects of being haploinsuffient for two different genes and how frequently such bigenic interactions compromise cell function.

To illustrate the utility of this new approach, the researchers examined nearly 5, 000 haploinsufficient yeast strains to identify over 200 genes that, in combination, cannot tolerate a reduction in gene copy number for the actin gene. “We knew that actin was an important gene, but we were still surprised at the large number of haploinsufficient interactions we uncovered. This test case suggests that similar interactions in complex organisms can have major influences on phenotypes such as the development and susceptibility to disease.”

This paper is one of the first examples of a large-scale reverse genetic screen that specifically looks at haploinsufficiency, and it is expected that this kind of systemic analysis will be particularly useful in uncovering complex genetic interactions in other organisms, including the study of complex, human genetic disorders.