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

PlantSynBio：破译作物调控 DNA 的语法以实现基因表达的精确工程

基本信息

批准号：
2240888
负责人：
Christine Queitsch
金额：
$ 200万
依托单位：
University of Washington
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2240888&HistoricalAwards=false
关键词：
PlantSynBio Deciphering grammar crop regulatory

项目摘要

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.

植物研究人员和潜水员一致认为，需要技术进步来满足对农产品的未来需求，尤其是鉴于气候危机的加速危机。尽管过去的传统植物育种和肥料的施用曾经产生了大量增加的农业产量，但近年来产量已经稳定下来。该项目使用新颖的基因组规模技术和高级分析方法来识别并表征成千上万的遗传元素，这些遗传元素驱动了玉米和番茄中的生长和环境弹性，这些作物代表了两种主要的植物。所得数据集的大尺寸可实现这些元素的系统计算分析，并允许设计具有理想特征的合成元素。这些设计用于未来作物工程的适用性和安全性将在实验室的玉米和番茄植物中进行检查。当今的植物研究人员和呼吸器需要精通进行基因组规模实验并采用先进的计算方法。该项目将为几名本科生和博士后研究员的培训和职业发展提供资金。对植物基因调节的了解有限，缺乏潜水员，植物来源的监管元素以驱动转基因的植物损坏了植物的合成生物学。为了促进植物合成生物学，该项目将采用大量平行的记者测定法和机器学习来破译玉米和番茄中基因调节元素的语法，包括增强剂，启动子，绝缘子和终结者，以及其对四种常见环境条件的局部相互作用。这些调节元素和元素组合的显着特征将通过卷积中性网络模型来识别，该模型将用于演变和设计具有所需特征的合成元素。设计的启动子和增强子元素以及植物来源的绝缘子和终端将成为合成生物学应用的基础。模型推断将在具有工程的天然调节元件的转基因作物中进行测试，并通过整合多基因记者盒的整合，其可调和可编程活性由合成调节元素驱动。 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 precious of support through evaluation using the Foundation's intellectual merit和更广泛的影响审查标准。