Collaborative Research: Multidimensional single-cell phenotyping for elucidating genome to phenome relationships

合作研究：用于阐明基因组与表型关系的多维单细胞表型分析

• 批准号: 2041523
• 负责人: Andreas Vasdekis
• 金额: $ 33.65万
• 依托单位: Regents of the University of Idaho
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2041523&HistoricalAwards=false
• 关键词: Collaborative; Research; Multidimensional; single; cell

The aim of this project is to develop methods and apply them to better understand how cells can optimally perform more than one task simultaneously, such as to grow and to synthesize biofuels at high quantities and efficiently. These findings are expected to accelerate ongoing efforts that employ biological systems as factories to produce high-value chemicals, and, thus, contribute to a more sustainable bioeconomy. This project will also offer exceptional training opportunities to high school and undergraduate students underrepresented in science, with a focus on transferring the mathematical rigor of physical and engineering sciences to biology. Further, this project is highly interdisciplinary, thus offering exceptional training opportunities to graduate students towards professional careers that address multifactorial societal needs.Systems biology has greatly improved our ability to program cells to perform a specific task. As the number of desired tasks increases, however, the complexity of biological systems restricts our ability to program or explore the foundation of cells that optimally perform multiple tasks simultaneously. This project will address this challenge via transformative microfluidic screening of combinatorial mutant libraries with single-cell resolution. Single-cell resolution will critically enable the selection of mutants directly from growing cultures, as well as quantify cellular noise. By applying the proposed method to an important biofuel platform and by combining the experimental results with genome-scale metabolic models, the project will generate fundamental knowledge on the genome-wide origins of multidimensional phenotypic traits and cell-to-cell phenotypic heterogeneity. This project is jointly funded by Systems and Synthetic Biology Cluster of the MCB Division and the Established Program to Stimulate Competitive Research (EPSCoR).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.

该项目的目的是开发方法并应用它们来更好地了解细胞如何同时最佳地执行多项任务，例如大量有效地生长和合成生物燃料。这些发现预计将加速正在进行的利用生物系统作为工厂生产高价值化学品的努力，从而为更可持续的生物经济做出贡献。该项目还将为在科学领域代表性不足的高中和本科生提供特殊的培训机会，重点是将物理和工程科学的数学严谨性转移到生物学中。此外，该项目是高度跨学科的，因此为研究生提供了特殊的培训机会，以解决多因素的社会需求的职业生涯。系统生物学大大提高了我们编程细胞执行特定任务的能力。然而，随着所需任务数量的增加，生物系统的复杂性限制了我们对同时最佳执行多项任务的细胞基础进行编程或探索的能力。该项目将通过具有单细胞分辨率的组合突变体库的变革性微流体筛选来应对这一挑战。单细胞分辨率将至关重要地使得能够直接从生长培养物中选择突变体，以及量化细胞噪声。通过将所提出的方法应用于一个重要的生物燃料平台，并将实验结果与基因组规模的代谢模型相结合，该项目将产生关于多维表型性状和细胞间表型异质性的全基因组起源的基础知识。 该项目由MCB部门的系统和合成生物学集群以及刺激竞争研究的既定计划（EPSCoR）共同资助。该奖项反映了NSF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。

项目成果

Scattered‐light‐sheet microscopy with sub‐cellular resolving power

具有亚细胞分辨率的散射光片显微镜

• DOI: 10.1002/jbio.202300068
• 发表时间: 2023
• 期刊: Journal of Biophotonics
• 影响因子: 2.8
• 作者: Subedi, Nava R.;Stolyar, Sergey;Tuson, Sabrina J.;Marx, Christopher J.;Vasdekis, Andreas E.
• 通讯作者: Vasdekis, Andreas E.