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., Cell 2026; 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’, and ‘Shred-seq’, multiplexed methods for generating and characterizing thousands of structural variants (SVs) in mammalian genomes with single-cell resolution. These methods enable 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; Koeppel et. al bioRxiv 2026
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: Pinglay et al., Cell 2026; Trolle et al., Elife 2022; McDiarmid et al., Nature Biotech 2025 ; Trolle et al., BioRxiv 2025
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.

Publications: Pinglay et al., Cell 2026; Pinglay, Nature 2026

We are a group of biological tinkerers at the intersection of synthetic genomics, genome engineering, single-cell sequencing and de novo design.

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

We are a group of biological tinkerers at the intersection of synthetic genomics, genome engineering, single-cell sequencing and de novo design.

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

Our focus areas include:

For a full list of publications, click here:

Our research is supported by:

1. Synthetic genomics to study mammalian gene regulation

2. Mammalian genome rearrangements and minimal genomes

3. Genome writing as a platform for cellular engineering

4. Designing, Building, Testing, and Learning from Synthetic Genomes

We are a group of biological tinkerers at the intersection of synthetic genomics, genome engineering, single-cell sequencing and de novo design.

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

Our focus areas include:

For a full list of publications, click here:

Our research is supported by: