Drug screens

2023 Feb 17

DRSC & DRTC Genetics and Genomics Workshop

(All day)

Location: 

Online
The DRSC is collaborating with the Drosophila Research and Training Center of Nigeria and the laboratory of Prof. Ross Cagan (University of Glasgow) to present an online workshop on Drosophila genomics and genetics.
Decorative cartoon drawn with BioRender depicting DRSC-BTRR technology concepts

So you want to do a CRISPR pooled screen in insect cells? You can! Here's how

May 12, 2022

At the DRSC-BTRR, we've been doing a lot of pooled-format CRISPR knockout screens in Drosophila cells. We're finding the results to be robust and reproducible. And best of all, the results have been informative, providing insights into diverse areas of biology.

Thinking about how to do CRISPR knockout screens in cells is a little different from thinking about how to do a genetic or RNAi screen in vivo or doing an arrayed-format RNAi screen....

Read more about So you want to do a CRISPR pooled screen in insect cells? You can! Here's how
Ulrike S Eggert, Amy A Kiger, Constance Richter, Zachary E Perlman, Norbert Perrimon, Timothy J Mitchison, and Christine M Field. 2004. “Parallel chemical genetic and genome-wide RNAi screens identify cytokinesis inhibitors and targets.” PLoS Biol, 2, 12, Pp. e379.Abstract

Cytokinesis involves temporally and spatially coordinated action of the cell cycle and cytoskeletal and membrane systems to achieve separation of daughter cells. To dissect cytokinesis mechanisms it would be useful to have a complete catalog of the proteins involved, and small molecule tools for specifically inhibiting them with tight temporal control. Finding active small molecules by cell-based screening entails the difficult step of identifying their targets. We performed parallel chemical genetic and genome-wide RNA interference screens in Drosophila cells, identifying 50 small molecule inhibitors of cytokinesis and 214 genes important for cytokinesis, including a new protein in the Aurora B pathway (Borr). By comparing small molecule and RNAi phenotypes, we identified a small molecule that inhibits the Aurora B kinase pathway. Our protein list provides a starting point for systematic dissection of cytokinesis, a direction that will be greatly facilitated by also having diverse small molecule inhibitors, which we have identified. Dissection of the Aurora B pathway, where we found a new gene and a specific small molecule inhibitor, should benefit particularly. Our study shows that parallel RNA interference and small molecule screening is a generally useful approach to identifying active small molecules and their target pathways.