NSF Postdoctoral Fellowship in Biology FY 2019: The Genomic Basis for Dysregulation of Protein Abundance in Maize

2019 财年 NSF 生物学博士后奖学金：玉米蛋白质丰度失调的基因组基础

• 批准号: 1906619
• 负责人: Joseph Gage
• 金额: $ 21.6万
• 依托单位: Gage, Joseph Lee
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1906619&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; FY

This action funds an NSF National Plant Genome Initiative Postdoctoral Research Fellowship in Biology for FY 2019. 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 Joseph Gage is "The Genomic Basis for Dysregulation of Protein Abundance in Maize" The host institutions for the fellowship are Cornell University and Washington University and the sponsoring scientists are Drs. Edward S. Buckler and Richard Vierstra.DNA sequences get translated into proteins, which are important components in determining an organism's size, shape, and health. Small differences in DNA sequence can cause large changes in how much of the resulting protein is made, but little is known about how those changes in DNA sequence affect protein quantity. To learn more about the relationship between DNA sequence and protein quantity, this research will measure the abundance of thousands of different proteins produced by twenty-seven diverse varieties of maize (corn). Genome sequences as well as gene expression levels will be used to learn how differences in DNA sequence result in differing amounts of protein. The data generated will be used to build machine learning models that can predict protein abundance from DNA sequence alone. The findings from this study will provide new insights into how complex traits (like an organism's size, shape, or health) are controlled by differences in DNA sequence spread throughout the genome. Broader impacts include mentoring and training undergraduate and graduate students as well as participating in the Skype-A-Scientist program (https://skypeascientist.com) which pairs scientists in various STEM disciplines with classrooms of children for question and answer sessions. Training objectives include obtaining expertise in bioinformatics, molecular genetics, proteomics, transcriptomics, application of machine learning, and functional genomics. Proteins are a crucial determinant of phenotype. As the ultimate step in the central dogma of molecular biology, their presence and abundance determine phenotypic state. To date, there are no published studies of proteomic variability between genetically diverse members of an economic important crop plant species. This project seeks to develop a model of how rare and deleterious alleles cause dysregulation of protein abundance by affecting translation, transport, and degradation via changes to protein structure and function in maize. This research will break new ground in maize functional genomics and proteomics by integrating pre-existing genomic data with newly generated time-series transcriptomic data and proteomic characterization of twenty-seven diverse maize inbred lines to generate a multi-omic dataset that captures all three levels of the central dogma of molecular biology: DNA, RNA, and protein. Since genomic variants can affect protein abundance by dysregulation of either transcription, translation, or both, transcript and protein abundance will be used together to assess specifically how genetic variants impact translation on a genome-wide scale. Genetic variants with influential effects on translation will be identified and characterized for their effects on protein secondary structure, solvent accessibility, contact between residues, and intrinsic disorder. These features will be used to formulate an overarching model to describe the influence of rare and deleterious variants on protein abundance. All proteomic and transcriptomic data generated for the twenty-seven diverse maize inbred lines will be useful for other projects and researchers, and for that reason, it is important that all data be as accessible and organized as possible. Raw reads from 3? RNA sequencing will be deposited on the NCBI-SRA (https://www.ncbi.nlm.nih.gov/sra), and the raw mass spectra from proteomic assays will be made available on the ProteomeXchange database (http://www.proteomexchange.org/). Transcript and protein abundance data will be made available through a DOI and hosted by CyVerse (https://www.cyverse.org/data-store). Keywords: gene expression, dysregulation of protein accumulation, sequencing, proteomics, modeling, maizeThis 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.

本行动资助NSF国家植物基因组计划2019财年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。约瑟夫·盖奇的研究和培训计划的标题是“玉米蛋白质丰度失调的基因组基础”该奖学金的主办机构是康奈尔大学和华盛顿大学，赞助科学家是dr。Edward S. Buckler和Richard Vierstra。DNA序列被翻译成蛋白质，蛋白质是决定生物体大小、形状和健康状况的重要组成部分。DNA序列的微小差异会导致产生的蛋白质数量的巨大变化，但人们对DNA序列的这些变化如何影响蛋白质数量知之甚少。为了更多地了解DNA序列和蛋白质数量之间的关系，这项研究将测量27种不同品种的玉米（玉米）产生的数千种不同蛋白质的丰度。基因组序列和基因表达水平将用于了解DNA序列的差异如何导致不同数量的蛋白质。生成的数据将用于构建机器学习模型，该模型可以仅从DNA序列预测蛋白质丰度。这项研究的发现将为研究复杂性状（如生物体的大小、形状或健康状况）是如何由遍布整个基因组的DNA序列差异控制的提供新的见解。更广泛的影响包括指导和培训本科生和研究生，以及参与Skype-A-Scientist计划（https://skypeascientist.com），该计划将各种STEM学科的科学家与儿童教室配对，进行问答环节。培训目标包括获得生物信息学、分子遗传学、蛋白质组学、转录组学、机器学习应用和功能基因组学方面的专业知识。蛋白质是表型的关键决定因素。作为分子生物学中心法则的最终步骤，它们的存在和丰度决定了表型状态。迄今为止，还没有发表的关于一种重要经济作物物种的遗传多样性成员之间蛋白质组变异性的研究。该项目旨在建立一个模型，揭示罕见和有害等位基因如何通过改变玉米蛋白质结构和功能，影响蛋白质的翻译、运输和降解，从而导致蛋白质丰度失调。这项研究将通过整合已有的基因组数据与新生成的时间序列转录组数据和27种不同玉米自交系的蛋白质组学特征，在玉米功能基因组学和蛋白质组学方面开辟新的领域，从而生成一个多组学数据集，该数据集涵盖了分子生物学中心法则的所有三个层面：DNA、RNA和蛋白质。由于基因组变异可以通过转录、翻译或两者的失调来影响蛋白质丰度，因此转录物和蛋白质丰度将一起用于评估遗传变异如何在全基因组范围内影响翻译。对翻译有影响的遗传变异将根据其对蛋白质二级结构、溶剂可及性、残基之间的接触和内在无序性的影响进行鉴定和表征。这些特征将用于制定一个总体模型来描述罕见和有害变异对蛋白质丰度的影响。为27个不同的玉米自交系生成的所有蛋白质组学和转录组学数据将对其他项目和研究人员有用，因此，所有数据尽可能地可访问和组织是很重要的。从3？RNA测序将存储在NCBI-SRA （https://www.ncbi.nlm.nih.gov/sra）上，蛋白质组学分析的原始质谱将在ProteomeXchange数据库（http://www.proteomexchange.org/）上提供。转录物和蛋白质丰度数据将通过DOI提供，并由CyVerse托管（https://www.cyverse.org/data-store）。关键词：基因表达，蛋白质积累失调，测序，蛋白质组学，建模，玉米该奖项反映了美国国家科学基金会的法定使命，并通过基金会的智力价值和更广泛的影响审查标准进行评估，认为值得支持。