NSF Postdoctoral Fellowship in Biology FY 2021: Deciphering grammatical rules of notochord enhancers and their role in notochord development in Ciona intestinalis

2021 财年 NSF 生物学博士后奖学金：破译脊索增强子的语法规则及其在海鞘脊索发育中的作用

• 批准号: 2109907
• 负责人: Krissie Tellez
• 金额: $ 13.8万
• 依托单位: Tellez, Krissie
• 依托单位国家: 美国
• 项目类别: Fellowship Award
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2109907&HistoricalAwards=false
• 关键词: NSF; Postdoctoral; Fellowship; Biology; FY

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2021, Integrative Research Investigating the Rules of Life Governing Interactions Between Genomes, Environment and Phenotypes. The fellowship supports research and training of the Fellow that will contribute to the area of Rules of Life in innovative ways. Early developmental stage cells differentiate into all of the cell types present in an organism’s adult body. These transitions are the result of changes in gene expression and the subsequent changes in RNA and protein products. Enhancers are genetic elements that encode instructions for the location and timing of gene expression, which ensures that tissues are created at the right time and place during development; variations in enhancer sequences are associated with outcomes that impact organisms in many ways. However, the millions of enhancer sequence variations have made it difficult to determine causal links between enhancer genotype and its expression (phenotype). The Fellow will investigate how control of gene expression is encoded within enhancers and the links between enhancers and these organismal traits. Research findings will be communicated by the Fellow to diverse audiences through mentorship of undergraduate student researchers and public science outreach programs.This research will examine tissue-specific enhancers in the notochord, an embryonic tissue that provides structural support and developmental patterning signals to adjacent tissues. To study how notochord activity is encoded within notochord-specific enhancers, the Fellow will create synthetic notochord enhancer variant reporter DNA constructs, which will be introduced into fertilized eggs of the sea squirt, Ciona intestinalis (Ciona). Ciona embryos will be screened for enhancer activity by measuring fluorescent reporter activity with microscopy and unique DNA barcode expression with RNA sequencing. The Fellow will use data generated from enhancer activity screens to identify common features of notochord enhancers. These notochord enhancer features will then be used to inform an existing computational pipeline to identify potential notochord enhancers within the Ciona genome. Additionally, the Fellow will use targeted gene editing in fertilized Ciona eggs to examine how genetic variations within notochord-specific enhancers impact gene expression (of genes controlled by selected enhancers) and notochord development (phenotype). Data generated from this research will be incorporated into interactive guest lectures for undergraduates; the Fellow will also gain training and experience in university-level teaching and mentorship, computational methods to analyze large data sets, and scientific communication.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.

该行动资助 2021 财年 NSF 生物学博士后研究奖学金，研究基因组、环境和表型之间相互作用的生命规则的综合研究。该奖学金支持研究员的研究和培训，为生命规则领域做出贡献。以创新的方式生命。早期发育阶段的细胞分化为生物体成人体内存在的所有细胞类型。这些转变是基因表达变化以及随后的 RNA 和蛋白质产物变化的结果。是编码基因表达位置和时间指令的遗传元件，确保组织在发育过程中在正确的时间和地点产生；增强子序列的变异与以多种方式影响生物体的结果相关。增强子序列变异使得确定增强子基因型与其表达（表型）之间的因果关系变得困难，该研究员将研究增强子内如何编码基因表达的控制以及增强子与这些生物性状之间的联系。通过指导，研究员向不同的受众本科生研究员和公共科学推广项目。这项研究将检查脊索中的组织特异性增强子，脊索是一种胚胎组织，为邻近组织提供结构支持和发育模式信号。研究员将创建合成脊索增强子变异报告 DNA 构建体，将其引入海鞘海鞘 (Ciona) 的受精卵中，并对 Ciona 胚胎进行增强子筛选。该研究员将使用增强子活性筛选生成的数据来识别脊索增强子的共同特征，然后将这些脊索增强子特征用于通知现有的计算流程。此外，该研究员还将在海鞘受精卵中使用靶向基因编辑来检查脊索特异性增强子中的遗传变异如何影响基因表达（由选定的基因控制）。这项研究产生的数据将被纳入本科生的互动客座讲座中；该研究员还将获得大学水平的教学和指导、分析大数据集的计算方法以及科学方面的培训和经验。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Diverse logics and grammar encode notochord enhancers

不同的逻辑和语法编码脊索增强子

• DOI: 10.1101/2022.07.25.501440
• 发表时间: 2022-07-27
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Benjamin P Song;Michelle F Ragsac;Krissie Tellez;Granton A. Jindal;Jessica L Grudzien;Sophia H Le;E. Farley
• 通讯作者: E. Farley