Grant: Operating Grant

Scientists now know that the ability of cells to grow and divide is governed by thousands of genes and that the function of genes is remarkably conserved from simple yeasts to human cells. Our group has pioneered methods that take advantage of the experimental accessibility of the yeast model system to understand how genes work together to create healthy cells or to produce a disease state. We have developed a unique robotics lab called GenNet that allows us to automate yeast genetic screens. We have used GenNet to produce the first maps of genetic interactions, providing a view of the 'wiring diagram' of a cell. We now propose to expand our GenNet platform to allow us to explore genetic interactions that are often associated with human diseases. We are particularly interested in understanding a phenomenon called genetic suppression in which lesions in one gene compensate for the deleterious effects of mutations in another. Suppression provides a powerful tool for identifying new relationships between genes and their corresponding pathways in the cell. Moreover, suppressors of mutations associated with a human disease gene represent potential targets for therapeutic intervention. So far, there have been no methods developed for systematic analysis of genetic suppression, and we aim to produce the first complete 'network' of genetic suppression for any organism. We expect that our diagram will be an invaluable tool for predicting genetic interactions relevant to many complex human diseases.