Department of Bioengineering Seminar Series Presents
Paul C. Blainey, Ph.D.
Massachusetts Institute of Technology Department of Biological Engineering and Broad Institute of Harvard and MIT
“High throughput genomic and chemical screening with imaging”
The Blainey lab develops and applies technology to access new information about biological systems and alleviate bottlenecks in data collection. I will present two examples:
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.
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.
Dr. Blainey took degrees in mathematics and chemistry at the University of Washington before joining Professors Gregory L. Verdine and X. Sunney Xie in the Department of Chemistry and Chemical Biology at Harvard University. There, Dr. Blainey elucidated the mechanics of proteins diffusing along DNA using single-molecule mechano-optical assays and earned a PhD in Physical Chemistry. Dr. Blainey transitioned to Professor Stephen R. Quake’s group at Stanford University, integrating active microfluidics, optical trapping, & new single-molecule microfluidic assays to enable single-cell microbial genomic sequencing. A faculty member in Biological Engineering at MIT and a Core Member of the Broad Institute since 2012, Dr. Blainey’s group integrates microfluidic, molecular, and imaging tools to prepare practical, robust, and scalable solutions to major challenges in next-generation sequencing sample preparation, single-cell analysis, genomic screening, and therapeutics development.
Light refreshments will be served.