Genetic Perturbation Program

Some will say that finding just the right wine to pair with a meal can improve even the finest cuisine, transforming a pleasant gustatory experience into something approaching perfection. But with potentially hundreds of wines to choose from, picking the “right” one can be a chore for the casual wine-lover. That’s where the sommelier comes in, applying expertise to curate a list of only the best pairings to suit one’s needs.

To fulfill this mission, GPP collaborates with researchers throughout the Broad community and beyond to apply functional genomics to biological discovery. This includes Broad flagship projects, such as the Dependency Map, and investigator-driven projects. Through these interactions, we gain critical insight into the strengths and limitations of existing approaches to functional genomics technologies, informing the further development of experimental tools.

For the past seven years, software engineering manager Tom Green has guided the development and maintenance of software tools that support the Genetic Perturbation Platform at the Broad Institute, where he can be found working with a team of software engineers or consulting with scientists conducting experimental screens. Two decades ago, however, Green was living without electricity or running water in the jungles of Nicaragua, a houseguest of locals in the remote village of Karawala on the Caribbean coast, doing a very different kind of research.

What: For patients with T cell acute lymphoblastic leukemia (T-ALL), a rare form of blood cancer that mainly affects children and young adults, drug resistance poses a major threat to a promising treatment option currently in clinical trials. About half of patients with T-ALL have mutations in NOTCH1, but drugs that target this gene have so far produced only short-lived effects: at first, the cancer seems to respond, but in a short period of time, T-ALL returns.

For decades, researchers have sought a biological toolset capable of precisely and systematically turning off genes throughout the genomes of human cells. The CRISPR-Cas9 system – a recently discovered system with bacterial origins – has the potential to overcome many of the limitations of currently available gene-silencing techniques. Earlier this year, several research groups showed that it was possible to use CRISPR-Cas9 to turn off genes in mammalian cells.