The American Association for the Advancement of Science (AAAS) premier journal, Science, features research from UCSF Urology’s Luke Gilbert, PhD and Jonathan Weissman, PhD from UCSF’s Department of Cellular and Molecular Pharmacology in their on-line publication released this week. The paper, “Exploring genetic interaction manifolds constructed from rich single-cell phenotypes” describes their approach to better understand genetic interactions in solving questions surrounding diseases.
“A central goal in biology is to determine how genes work together to produce complex biological systems,” explains Gilbert. “Despite this, it has been remarkably hard to systematically find or understand genetic interactions that drive complex human cell behaviors.”
In the paper, Gilbert and Weissman describe a new way to systematically identify genetic interactions and then to understand how specific genes work together to control the function of human cells. This approach first uses a modified form of CRISPR to activate the expression of many thousands of gene pairs revealing gene pairs that function together to control cellular activity. This new platform then takes hundreds of interesting gene pairs and analyzes the mechanism of each genetic interaction using single cell RNA sequencing. This second step of the new technology reveals how these genes are functioning together to control cell behavior which is a critical step that is important for most medical applications. Lastly, the authors show that by incorporating information from each stage of this genetic interaction analysis that they can predict genetic interactions which should greatly enable application of this approach to rapidly search for key gene pairs in the future. Importantly, this technology will reveal innovative strategies for killing tumor cells, identify new routes to activate the immune system to fight cancer or infection and also enable regenerative medical applications enabled by cellular engineering.
For more information on the Gilbert Lab and CRISPR click here.