NSF Postdoctoral Fellowship in Biology: Tools for engineering rice gene expression

本行动资助2023财年美国国家科学基金会植物基因组生物学博士后研究奖学金。该奖学金支持奖学金获得者在主办实验室的研究和培训计划，该奖学金获得者还提出了扩大生物学参与的计划。丁大卫本次奖学金的研究和培训计划题目为“植物基因表达工程工具”。该奖学金的主办机构是加州大学伯克利分校，赞助科学家是大卫·萨维奇博士。作物工程为解决预计的粮食需求增长和气候变化带来的挑战提供了一条途径。最近的基因编辑工具在原则上实现了这一点，但由于缺乏对突变如何映射到感兴趣的表型结果（包括增加的光合能力、抗旱性或氮利用效率）的理解，它们对作物改良的潜力受到限制。重要的是，调整特定目标基因的表达可以改善这些性状，这表明理解和发现能够合理调整蛋白质丰度的基因组突变可能足以改善作物。总体而言，该项目开发了了解植物调控突变的缺失工具，并可能帮助开创一个新时代，在这个新时代，基因编辑技术——与缓慢和人工育种工作相反——可以快速创造新的作物品种，解决整个社会的基本粮食安全和可持续性问题。奖学金获得者的训练目标不仅包括进一步发展技术、分析和综合技能，还包括沟通和教学技能。该研究员目前正在并将继续通过参加塔马尔佩斯山学院的志愿服务机会来传达科学探究的兴奋和有用性，该学院是一个为圣昆廷州立监狱的学生提供负担得起的高等教育的组织。在这个项目中，将开发一个计算管道，结合高通量微扰实验分析，以克服理解植物基因调控变异固有的缓慢和低通量性质。通过关注已验证的基因集，对调控突变的理解可以使基因编辑酶同时调整多个靶基因丰度，并且，由于许多已知的靶基因参与正交途径，可以使所需性状的加性或协同增加，以及对多个性状的改进，在一个步骤中。这项工作的结果将通过出版物共享，任何生成的原始数据和分析管道都将向公众开放（通过序列读取存档和GitHub: https://www.ncbi.nlm.nih.gov/sra, www.github.com），以实现可重复性和作为工具。所有创建的材料将根据要求提供。通过这种方式，每个人都可以访问这个项目产生的任何资源。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This action funds an NSF Plant Genome Postdoctoral Research Fellowship in Biology for FY 2023. The fellowship supports a research and training plan in a host laboratory for the Fellow who also presents a plan to broaden participation in biology. The title of the research and training plan for this fellowship to David Ding is "Tools for engineering plant gene expression". The host institution for the fellowship is UC Berkeley and the sponsoring scientist is Dr. David Savage.Crop engineering offers a path to address the projected increases in food demand and challenges arising from a changing climate. Recent gene editing tools enable this in principle, but their potential for crop improvement is limited by the lack of understanding of how mutations map to phenotypic outcomes of interest, including increased photosynthetic capacity, drought resistance, or nitrogen-use efficiency. Importantly, tuning the expression of particular target genes can improve such traits, suggesting that understanding and finding genomic mutations that enable rational tuning of protein abundances could be sufficient for crop improvement. Overall, this project develops the missing tools to understand regulatory mutations in plants and could help usher in a new era in which gene editing technology – in contrast to slow and manual breeding efforts – could enable the rapid creation of novel crop varieties addressing fundamental food security and sustainability issues for society at large. The training objectives for the Fellow include not just further developing technical, analytical, and synthesis skills, but also communication and teaching skills. The Fellow currently does and will continue to convey the excitement and usefulness of scientific inquiry by participating in volunteering opportunities at Mount Tamalpais College, an organization that provides access to affordable higher education to students incarcerated at San Quentin State Prison.In this project, a computational pipeline, coupled with high-throughput perturbative experimental assays, will be developed to overcome the inherently slow and low-throughput nature of understanding gene regulatory variants in plants. By focusing on validated sets of genes, the resulting understanding of regulatory mutations could enable simultaneous tuning of multiple target gene abundances with gene editing enzymes, and, since many known target genes participate in orthogonal pathways, could enable additive or synergistic increases in desired traits, as well as an improvement towards multiple traits, in a single step. Findings resulting from this work will be shared through publications, with any generated raw data, and analysis pipelines made available to the general public (through the sequence read archive and GitHub: https://www.ncbi.nlm.nih.gov/sra, www.github.com) for reproducibility and as tools. All created materials will be made available upon request. In this way, everyone will have access to any resources generated from this project.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.