We have developed tools for ‘genome writing’ in mammalian cells which involves the bottom-up synthesis and site-specific delivery of large (>100kb) DNA constructs. This approach facilitates multiplex editing over large genomic windows enabling the study of how regulatory elements interact to specify gene expression patterns during development. We are now scaling these studies by combining large-scale DNA synthesis with single-cell sequencing.

Publications:
Pinglay et al., Science 2022; Mitchell et al., Genetics 2021; Brosh et al., PNAS 2021; German et al., BioRxiv 2022.

We have recently developed ‘Genome-shuffle-seq’, a multiplexed method for generating and characterizing thousands of structural variants (SVs) in mammalian genomes with single-cell resolution. This method enables large-scale screens to assess the impact of structural genome alterations in developmental contexts and cancer models. Ultimately, we aim to identify dispensable genomic regions, paving the way for minimal mammalian genomes that could serve as universal chassis for cell therapy.

Publications: Pinglay et. al Science 2025

We are leveraging our expertise in synthesizing and integrating large DNA constructs to introduce sophisticated genetic programs into mammalian cells, enabling them to exhibit novel behaviors.

Our work focuses on two key areas:

• Developing multiplexed methods to rapidly discover solutions to complex biological engineering challenges.

• Collaborating with the Seattle Hub for Synthetic Biology to engineer cells that can record their own histories directly into their genomes.

Publications: Trolle et al., Elife 2022; McDiarmid et al., BioRxiv 2024

We are developing methods to overcome critical challenges in the design, construction, testing, and analysis of synthetic genomes. Our long-term objective is to create fully synthetic genomes that redefine the limits of natural genome design and functionality.