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At Twist Bioscience, we work in service of customers who are changing the world for the better. In fields such as medicine, agriculture, industrial chemicals and data storage, by using our synthetic DNA tools, our customers are developing ways to better lives and improve the sustainability of the planet. The faster our customers succeed, the better for all of us, and Twist Bioscience is uniquely positioned to help accelerate their efforts. Our innovative silicon-based DNA Synthesis Platform provides precision at a scale that is otherwise unavailable to our customers. Our platform technologies overcome inefficiencies and enable cost-effective, rapid, precise, high-throughput synthesis and sequencing, providing both the quality and quantity of the tools they need to rapidly realize the opportunity ahead.

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Discovering PARP inhibitor resistance mechanisms using genome-wide and focused CRISPR screens

Stephen Pettitt, PhD

In this webinar, Dr. Stephen Pettitt explains how he applies genome-wide targeted mutagenesis screens to elucidate the genetic basis of drug resistance. Using mouse and breast cancer cell lines, Dr. Pettitt’s team developed a targeted, genome-wide mutagenesis screen to identify mutations responsible for resistance to the potent PARP inhibitor talazoparib (BMN 673). The screen yielded one particularly interesting point mutation in the PARP1 gene. This mutation disrupted the ability of PARP1 to bind DNA, demonstrating that DNA binding is necessary for the action of talazoparib. Dr. Pettitt will describe how he then employed a high-density, focused sgRNA library targeting PARP1 to generate further mutants that he used to elucidate details of the structure-function relationships of PARP1. This research is not only important for unravelling the mechanisms underlying drug resistance, but it may improve future treatment plans for cancer patients.

In this webinar, you will learn:

  • How to use genome-wide CRISPR screening for mutant discovery
  • How to create a highly diverse, sgRNA library from Twist Bioscience for targeted, subtle mutations
  • How knowledge of the structure-function relationships of PARP1 mutants can inform treatment of cancer patients with these drugs

[Twist Bioscience] Webinar Sept 23 2018 Discovering PARP inhibitor

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