Scientists Build 'Speed Scanner' to Test Thousands of Plant Gene Switches at Once

After developing the approach, the team demonstrated its unprecedented speed for real-world investigations. They used ENTRAP-seq to study gene regulation in a transcription activator known to mediate expression of a gene that controls flowering in Arabidopsis, a plant used as a model organism for botany research. They created 350 mutant versions of the protein and quickly screened which ones could tune flowering time up or down.

"This experiment took just a few weeks. In contrast, for a previous study, our team characterized the activity of 400 plant transcription regulators, which took two people full time over two years using the conventional, brute force approach of testing things one by one," said lead author Patrick Shih, Deputy Vice President, Feedstocks Division and Director of Plant Biosystems Design at JBEI.

Shih and his team generated potential activator designs for this study using an existing AI model that identifies DNA sequences that could encode gene activating proteins from any organism.

"The model's predictions allowed us to focus our experimental efforts on the most informative proteins across thousands of genomes," said co-first author Lucas Waldburger, a graduate student researcher at UC Berkeley and JBEI.

However, the accuracy of this model is limited by a scarcity of training data because, as the scientists know firsthand, methods to investigate transcription regulators used to be punishingly slow. With ENTRAP-seq, researchers will be able to quickly generate huge datasets that can refine these models. And better models mean that those researchers can quickly scan a plant's genome and discover where all the gene switches are encoded - information that is nearly nonexistent for many species. Then, completing the positive feedback loop, ENTRAP-seq will help scientists study the effects of natural and engineered variations in those proteins to create versions that enhance desired traits.

"We're looking for all the switches and we want to know, are they on or off switches? And then, how far up and how far down can it go? Cataloging all of that will be a huge advance," said Shih, who is also associate professor at UC Berkeley and faculty scientist in Berkeley Lab's Biosciences Area. "Then maybe we find an important switch for making bigger plants, higher yields, or more stress resilient crops, and finally: can we crank that dimmer switch to 11?"

ENTRAP-seq is available for licensing through Berkeley Lab's Intellectual Property Office. This research was funded by the DOE Office of Science.

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