CAREER: Deciphering temporal events in mammalian cells using synthetic biology

职业：利用合成生物学破译哺乳动物细胞中的时间事件

• 批准号: 1553356
• 负责人: Wilson Wong
• 金额: $ 50.22万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-15 至 2022-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1553356&HistoricalAwards=false
• 关键词: CAREER; Deciphering; temporal; events; mammalian

1553356Wong, Wilson A fundamental goal in biology is to understand how cells make decisions when faced with external signal. The proposed work will seek to understand how a cell, through genetic programs found in its genome, can distinguish signals that are varying in time (dynamics) and generate different outcomes. A 'learning by building' approach will be used to engineer genetic systems that can decode dynamic signals. Specifically, the PI will engineer novel genetic programs in living mammalian cells to enable it to interpret signal duration and sequence. This approach will also provide a unique opportunity to bridge basic and applied science, where the novel genetic systems may be used in commercial applications. A broader goal of this proposed work is to inspire students to design living cells, and train the next generation of workforce skilled in genetic engineering to address challenges in health, food, energy, and environment. The education and outreach plans of this proposed work will accomplish these objectives by providing direct and stimulating research experience for undergraduates and underprivileged high school students, and developing classroom and laboratory based courses for students, high school teachers, and researchers.This CAREER proposal aims to understand how genetic networks process information. Such understanding will provide insight into a wide range of cellular processes. The proposed work will seek to delineate the governing rules of genetic circuits that decipher dynamic signals and produce divergent output states with limited inputs. In particular, two dynamical features, cumulative signal duration and temporal-order will be studied. A forward engineering approach will be used to explore genetic circuits that can decode dynamics. Specifically, the PI will (i) develop DNA recombinase-based cascade circuits to decode signal duration, and (ii) engineer and characterize two-input recombinase-based temporal-order sensing circuits. A broader goal of this proposed work is to inspire students to design living cells, and train the next generation of workforce skilled in synthetic biology to address challenges in health, food, energy, and environment. The education and outreach plans will accomplish these objectives by providing mentored laboratory-based research experience for undergraduates and underprivileged high school students, and by developing classroom and laboratory based courses for students, high school teachers, and researchers.This CAREER award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.

生物学的一个基本目标是了解细胞在面对外部信号时如何做出决定。这项提议的工作将寻求理解细胞如何通过在其基因组中发现的遗传程序来区分随时间（动态）变化的信号并产生不同的结果。一种“通过构建来学习”的方法将被用于设计能够解码动态信号的遗传系统。具体来说，PI将在活的哺乳动物细胞中设计新的遗传程序，使其能够解释信号的持续时间和序列。这种方法还将为基础科学和应用科学之间的桥梁提供一个独特的机会，在应用科学中，新的遗传系统可能用于商业应用。这项工作的一个更广泛的目标是激励学生设计活细胞，并培养下一代熟练的基因工程劳动力，以应对健康、食品、能源和环境方面的挑战。这项工作的教育和推广计划将通过为本科生和贫困高中学生提供直接和刺激的研究经验，并为学生、高中教师和研究人员开发课堂和实验室课程来实现这些目标。这个CAREER提案旨在了解基因网络如何处理信息。这样的理解将提供对广泛的细胞过程的洞察。拟议的工作将试图描述遗传电路的控制规则，这些规则可以破译动态信号，并在有限的输入下产生不同的输出状态。特别是两个动态特征，累积信号持续时间和时间顺序将被研究。正向工程方法将用于探索可以解码动力学的遗传电路。具体来说，PI将(i)开发基于DNA重组酶的级联电路来解码信号持续时间，以及（ii）设计和表征基于双输入重组酶的时序传感电路。这项提议的工作的一个更广泛的目标是激励学生设计活细胞，并培养下一代熟练的合成生物学劳动力，以应对健康，食品，能源和环境方面的挑战。教育和推广计划将通过为本科生和贫困高中学生提供指导的实验室研究经验，并为学生、高中教师和研究人员开发课堂和实验室课程来实现这些目标。该职业奖由CBET部门的生物技术和生化工程项目颁发，由分子和细胞生物科学部的系统和合成生物学项目共同资助。