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CPLC Seminar: "Advancing genomic and screening technologies for the life sciences”

Event Type
Department of Physics and CPLC
144 Loomis
Mar 30, 2018   2:00 pm  
Paul Blainey, MIT/Broad
Sarah Holmes
Originating Calendar
Physics - Biological Physics (CPLC/iPoLS) Seminar

The Blainey lab develops ways to access new information about biological systems and alleviate bottlenecks in data collection workflows. I will present examples in three activity areas:

Integrated sample prep for highly deployable genomics. Readout by next-generation sequencing (NGS) no longer limits throughput for many project types, but clinical applications demand low input quantities and streamlined workflows. To meet this demand, we developed a family of lab-on-a-chip microfluidic systems to realize major advances in real-world throughput, cost, and sensitivity by integrating entire sample preparation workflows from crude biological samples for whole genome shotgun and RNA-sequencing at the micro-scale, including direct-from-cells capability

High quality single cell genome sequencing. Microfluidics and whole-genome amplification are enabling single-cell genomics. At the same time, these technologies limit single-cell genomic studies by imposing cost and complexity (microfluidics) and limiting data quality (whole-genome amplification). Here I will present two new methods for single-cell genome analysis, one that requires no microfluidics or specialized equipment for direct single-cell genome amplification and another that leverages culture-based amplification rather than biochemical amplification to enable precise study of de novo mutations in single human cells

New scalable chemical and genomic screening technology. Droplet microfluidics methods are dramatically increasing the throughput of single-cell genomics assays. However, such methods have not yet impacted drug discovery due to small molecule crosstalk between droplets, particularly for more hydrophobic drug-like molecules. I will describe a new platform for processing and tracking tens of thousands of droplets in parallel that prevents crosstalk of small hydrophobic solutes. Beyond sequencing naturally occurring nucleic acids, functional genomics applies artificial genome perturbation and phenotype determination to identify gene functions. In forward genetic screens, efficient pooled methods for genome-wide screening are now popular, but require physical separation of selected cells for readout by amplicon sequencing. Many disease processes are characterized by complex cellular phenotypes that are best analyzed by high-content imaging assays. Here we present work using in-situ sequencing to combine major advantages of pooled approaches with high content imaging assays.

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