Pinglay Lab

We are a laboratory of biological tinkerers at the intersection of DNA synthesis, protein design and single-cell sequencing.

The Seattle Hub for Synthetic Biology is a collaboration between Allen Institute, Chan Zuckerberg Initiative and the University of Washington.

The Pinglay Lab is hosted at the Seattle Hub for Synthetic Biology and is part of the University of Washington, Department of Genome Sciences and the Brotman Baty Institute for Precision Medicine. We focus on developing technologies at the intersection of mammalian genome engineering, large-scale (>100kb) DNA synthesis, single-cell sequencing and de novo protein design.

In particular, we have developed tools for:

Mammalian ‘genome writing’ at the megabase scale that allows us to 1) rewrite existing genomic loci to understand how they work and 2) to endow cells with sophisticated behaviors using large amounts of novel genetic information.
Shuffling mammalian genomes to model the impact of genome rearrangements in human populations (structural variants), evolution and disease states such as cancer.

With these tools, we aim to construct improved disease models, elucidate the mechanisms of gene regulation, probe the limits of genome structure and to encode novel functionalities into mammalian cells for applications in biological recording, biologics production, cell therapy and cultivated meat.

Sudarshan Pinglay, Ph.D, leads a research lab affiliated with the University of Washington, Department of Genome Sciences, the Brotman Baty Institute for Precision Medicine and the Seattle Hub for Synthetic Biology.

Research Details

Dissecting the regulatory logic of mammalian gene regulation using large-scale DNA synthesis and single-cell sequencing

Despite the description of over 1 million cis-regulatory elements such as enhancers, insulators, promoters and silencers in mammalian genomes, the logic of how these (CREs) interact to specify a gene expression program has remained obscure.
We are developing technologies to increase the scale at which we can probe the logic of mammalian gene regulation by cis-regulatory elements such as enhancers using a combination of large-scale (>100kb) DNA synthesis and single-cell sequencing.
In addition, we have established a synthetic platform to study the interactions between cis- and trans- regulatory factors in the establishment and maintenance of new transcriptional states during development.

Mapping the consequences of mammalian genome rearrangements and paving the path to minimal genomes

We have recently developed Genome-shuffle-seq, a method that allows us to inducibly generate thousands of large structural variants to mammalian genomes and study their impact with single-cell resolution.
This method is currently being applied to understand the impact of large rearrangements on gene expression in varied developmental contexts and in modeling certain aspects of cancer progression.
We seek to identify regions of the genome that are dispensable for cell function, with the hope of minimal mammalian genomes that may serve as universal chassis for cell therapy.

Genome writing for biological recording

See Build Team page for more details