Dynamic Multiplexed Control and Modeling of Optogenetic Systems Using the High-Throughput Optogenetic Platform, Lustro

Harmer, Zachary P.; Thompson, Jaron C.; Cole, David L.; Venturelli, Ophelia S.; Zavala, Victor M.; McClean, Megan N.

doi:10.1021/acssynbio.3c00761

Title: Dynamic Multiplexed Control and Modeling of Optogenetic Systems Using the High-Throughput Optogenetic Platform, Lustro

Journal Article · 28 April 2024 · ACS Synthetic Biology

DOI: https://doi.org/10.1021/acssynbio.3c00761 · OSTI ID:2469990

Harmer, Zachary P. ^[1]; Thompson, Jaron C. ^[1]; Cole, David L. ^[1];

^[1];

^[2];

^[1]

Univ. of Wisconsin, Madison, WI (United States)
Univ. of Wisconsin, Madison, WI (United States); Argonne National Laboratory (ANL), Argonne, IL (United States)

The ability to control cellular processes using optogenetics is inducer-limited, with most optogenetic systems responding to blue light. To address this limitation, we leverage an integrated framework combining Lustro, a powerful high-throughput optogenetics platform, and machine learning tools to enable multiplexed control over blue light-sensitive optogenetic systems. Specifically, we identify light induction conditions for sequential activation as well as preferential activation and switching between pairs of light-sensitive split transcription factors in the budding yeast, Saccharomyces cerevisiae. We use the high-throughput data generated from Lustro to build a Bayesian optimization framework that incorporates data-driven learning, uncertainty quantification, and experimental design to enable the prediction of system behavior and the identification of optimal conditions for multiplexed control. This work lays the foundation for designing more advanced synthetic biological circuits incorporating optogenetics, where multiple circuit components can be controlled using designer light induction programs, with broad implications for biotechnology and bioengineering.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2469990

Journal Information:: ACS Synthetic Biology, Journal Name: ACS Synthetic Biology Journal Issue: 5 Vol. 13; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Dynamic Multiplexed Control and Modeling of Optogenetic Systems Using the High-Throughput Optogenetic Platform, Lustro

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