Paul Blainey, Biological Engineering, MIT

Host: Iwijn De Vlaminck

Integrating optics, microfluidics, and genomics to understand how genes and cells work

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

High quality single cell genome sequencing. Whole-genome amplification is enabling single-cell genome sequencing.  At the same time, biochemical amplification approaches limit single-cell genomic studies by degrading data quality. I will present a method that leverages culture-based amplification to enable precise study of de novo mutations in single human cells and report the initial findings from our pilot study.

Scalable chemical screening technology. Droplet microfluidics methods are dramatically increasing the throughput of single-cell genomics assays.  However, droplet approaches have not yet impacted drug discovery due to small molecule crosstalk between droplets. I will describe a new platform for processing and tracking tens of thousands of droplets in parallel that prevents crosstalk of small hydrophobic solutes and report results from a combination screen for antibiotic potentiation.

Pooled optical genomic screening in human cells. Forward genetic screens apply perturbations to the genome to identify the genetic basis of phenotypes of interest. Efficient pooled methods for genome-wide screening are becoming popular, but require physical separation of selected cells for readout by next-generation sequencing. Many disease processes are characterized by complex cellular phenotypes that are best analyzed by high-content imaging assays, but there has been no method to practice image-based phenotyping in pooled formats.  Here we present our work adapting in-situ sequencing for perturbation readout by microscopy and a demonstration screen for factors that affect NF-kB activation in stimulated human cells.

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