Serena Silver conducts a symphony of RNA silence
As a post-doctoral researcher in Harvard Medical School investigator (and Broad Associate Member) Norbert Perrimon's lab, Serena Silver loved talking to her fellow post-docs about their projects and liked to help them come up with new ideas to try. Now, as Group Leader of RNAi Screening Projects at the Broad, Serena gets to talk to researchers about their projects for a living.
"I really enjoyed listening at lab meetings and thinking through the projects and the controls needed for an experiment - that I get to do that as my job now is extremely satisfying," she says.
The RNAi Platform is helping researchers with projects related to cancer, infectious disease, metabolism, mitochondrial biology, type 2 diabetes, myocardial infarction, and more. RNA interference is a powerful tool because it allows researchers to "silence" genes. When a small piece of RNA that has been looped back upon itself (known as a small hairpin RNA or shRNA) is inserted into a cell, it causes cellular machinery to break down messenger RNA that matches this inserted piece. (Messenger RNA carries the instructions or "message" needed to create a protein; without it, the cell may be unable to produce a specific protein.) This gives researchers the ability to turn off a gene and see how a cell's behavior or characteristics change as a result. By using a library of shRNAs, researchers can turn off thousands of individual genes, one at a time, and look for certain effects of interest (for instance, altered response of an immune cell to pathogens, increased growth of axons from neurons, or increased resistance of a cancer cell to a chemotherapy agent.) These experiments, or screens, help researchers find a subset of genes important for a biological process of interest.
One thing that makes the RNAi Platform at Broad distinct from other RNAi screening operations is that its researchers not only use RNAi tools, but also create them. "We have several projects looking at performance of our libraries," says Serena. "The feedback from our research and also from our collaborative screens can then influence which reagents and tools we make next.”
Influenced by this feedback, Serena and her colleagues at the Broad are building a collection to complement the RNAi library, in collaboration with the Center for Cancer and Systems Biology at Harvard Medical School. Just as the RNAi library allows researchers to turn genes off one at a time, this complementary collection, known as an ORF library, allows researchers to turn individual genes on.
Since Serena joined the Broad, the RNAi Platform has grown in both size and scope. "When I started, the Platform focus was ready to expand, to encompass screening in addition to library creation. I was the first full-time screening scientist," she says. "Now there are five of us who work with screeners and we can engage with the dozens of Broad researchers who come to us with exciting questions and ideas and put our RNAi tools to work."