PlantSynBio: Deciphering the grammar of crop regulatory DNA for precise engineering of gene expression

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Plant researchers and breeders agree that technological advances are needed to meet the future demands for agricultural products, especially in light of the accelerating climate crisis. Although traditional plant breeding and fertilizer application have produced large increases in agricultural yields in the past, yields have plateaued in recent years. This project uses novel genome-scale technology and advanced analysis methods to identity and characterize the tens of thousands of genetic elements that drive growth and environmental resilience in maize and tomato, crops that represent two major classes of plants. The large size of the resulting data sets enables systematic computational analyses of these elements and allows for design of synthetic elements with desirable features. The applicability and safety of these designs for future crop engineering will be examined in maize and tomato plants in the laboratory. Today’s plant researchers and breeders need to be fluent in conducting genome-scale experiments and applying advanced computational methods. This project will provide funds for the training and the career development of several undergraduate students and postdoctoral fellows.The limited understanding of plant gene regulation and lack of diverse, plant-derived regulatory elements to drive transgenes have hampered plant synthetic biology. To facilitate plant synthetic biology, this project will apply massively parallel reporter assays and machine learning to decipher the grammar of gene-regulatory elements in maize and tomato, including enhancers, promoters, insulators and terminators, and their local interactions in response to four common environmental conditions. The salient features of these regulatory elements and element combinations will be identified by convolutional neural network models, which will be used to evolve and design synthetic elements with desired features. Designed promoter and enhancer elements, along with plant-derived insulators and terminators, will serve as building blocks for synthetic biology applications. Model inferences will be tested in transgenic crops with engineered native regulatory elements and through the integration of multi-gene reporter cassettes whose tunable and programmable activity is driven by synthetic regulatory elements. This project’s results will propel plant gene regulation and crop synthetic biology beyond current knowledge and tools, and jumpstart crop engineering efforts.This award was co-funded by the Plant Genome Research Program in the Division of Integrative Organismal Systems and the Systems and Synthetic Biology cluster in the Division of Molecular and Cellular Biosciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.