CAREER: Uncovering Quantitative Design Principles of RNA Regulators For Synthetic Biology
职业:揭示合成生物学 RNA 调节剂的定量设计原理
基本信息
- 批准号:1650040
- 负责人:
- 金额:$ 57.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2021-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Nontechnical Description: Cells have an amazing ability to process information, make decisions, and change their state in response to changing environments. This ability is encoded within the cellular DNA genome, which is converted into RNA and protein molecules through the basic processes of gene expression. Among the many functions these RNAs and proteins perform is regulating their own expression. In fact RNAs are now known to regulate almost all aspects of gene expression, and play central roles in controlling some of life's most basic processes. A key question in biotechnology and synthetic biology is then: How can RNA molecules be designed to control the expression of target genes inside cells to facilitate applications ranging from using cells as chemical factories all the way to using them as environmental sensors? As with many biomolecules, RNA function is intimately related to its structure. In this work, the investigator builds off of his development of a new small synthetic RNA mechanism called Small Transcription Activating RNAs, or STARs. STARs are hypothesized to allow the construction of unique gene expression control techniques since they represent a brand new function for sRNAs. This project seeks to use STARs as a test-bed for uncovering the principles for engineering RNA molecules to precisely control gene expression inside cells. This work will help realize the potential of RNA as a powerful substrate for cellular engineering. It will also shed new light on our scientific understanding of the fundamental sequence/structure/function relationship that underlies RNA's central role in natural biological systems. The projected studies and research training activities are thus expected to have a broad impact on society, ranging from the science of cellular gene regulation and the engineering science of RNA gene regulation that can directly connect to a broad array of biotechnological applications. This project will also cultivate the next generation of highly trained graduate students and teachers of synthetic biology who will be introduced to the broad, interdisciplinary nature of biotechnology research. Moreover, this program will actively engage the broader community to help create an informed public that is equipped to make important decisions about the future of synthetic biology.Technical Description: The overall goal of this project is to build an integrated research and education program focused on uncovering quantitative design principles that link small RNA sequence, structure, and function, and to use these principles to design synthetic RNAs that can precisely regulate gene expression. The education plan focuses on integrating research into the training of the next generation of synthetic biology students and teachers, and informing and exciting the broader public about synthetic biology.Trans-acting bacterial small RNAs (sRNA) exert regulation via direct RNA-RNA interactions with target messenger RNAs (mRNAs) that cause structural changes in the target. These changes in turn regulate many aspects of gene expression including transcription, translation and mRNA degradation. The central hypotheses of this project are that: 1) quantitative sRNA structure/function design principles can be discovered and used to rationally optimize and expand the functionality of RNA regulators, and 2) circuit-level design rules can be discovered and used to engineer new synthetic RNA genetic modules that control the timing and pattern of gene expression. The central goal of this CAREER project is to use Small Transcription Activating RNAs (STARs) as a test-bed for uncovering the quantitative design principles of RNA regulators for synthetic biology. This will be pursued using a multi-faceted approach that includes using cutting-edge RNA structure measurement technologies to elucidate the molecular level design principles of STARs. Once molecular-level principles are learned, the project will focus on using these techniques to learn the design rules for integrating STARs into decision making regulatory networks. In addition, new experiments and computational tools that can quantitatively model the kinetics of gene expression mediated by STARs will be used to understand how different aspects of STAR function propagate through RNA networks. Successful completion of these studies will forward the broader goal of creating a quantitative discipline of biological design that can be used to program cellular systems to solve important problems in sustainable energy, and biomanufacturing. In addition, the work may provide insight to mechanisms of native small RNA regulation of naturally occurring biological systems.Educational activities include developing a long term plan for the continuation of the Cold Spring Harbor Synthetic Biology summer course as a training center for a broad range of students and teachers across the globe; developing quantitative curricular materials for training future generations of synthetic biologists; and performing hands-on activities aimed towards families with school-age children to excite and inform them about synthetic biology.
非技术描述:细胞有一种惊人的能力,可以处理信息,做出决定,并根据不断变化的环境改变自己的状态。这种能力被编码在细胞DNA基因组中,并通过基因表达的基本过程转化为RNA和蛋白质分子。这些rna和蛋白质的许多功能之一是调节它们自己的表达。事实上,rna现在被认为可以调节基因表达的几乎所有方面,并在控制一些生命最基本的过程中发挥核心作用。因此,生物技术和合成生物学的一个关键问题是:如何设计RNA分子来控制细胞内靶基因的表达,以促进从将细胞用作化学工厂到将其用作环境传感器的各种应用?与许多生物分子一样,RNA的功能与其结构密切相关。在这项工作中,研究者建立了一种新的小合成RNA机制,称为小转录激活RNA,或STARs。由于它们代表了sRNAs的一种全新功能,因此假设STARs允许构建独特的基因表达控制技术。该项目旨在将STARs作为揭示RNA分子工程原理的试验台,以精确控制细胞内的基因表达。这项工作将有助于实现RNA作为细胞工程强大底物的潜力。它还将为我们对RNA在自然生物系统中发挥核心作用的基本序列/结构/功能关系的科学理解提供新的线索。因此,预计的研究和研究培训活动将对社会产生广泛的影响,范围从细胞基因调控科学和RNA基因调控的工程科学,可以直接连接到广泛的生物技术应用。该项目还将培养下一代训练有素的合成生物学研究生和教师,他们将了解生物技术研究的广泛、跨学科性质。此外,该计划将积极参与更广泛的社区,以帮助建立一个知情的公众,有能力对合成生物学的未来做出重要决定。技术描述:该项目的总体目标是建立一个综合的研究和教育计划,重点是揭示连接小RNA序列,结构和功能的定量设计原则,并利用这些原则设计可以精确调节基因表达的合成RNA。教育计划的重点是将研究整合到下一代合成生物学学生和教师的培训中,并向更广泛的公众提供有关合成生物学的信息和激励。反式作用细菌小rna (sRNA)通过与目标信使rna (mrna)的直接RNA-RNA相互作用发挥调控作用,导致目标的结构变化。这些变化反过来调节基因表达的许多方面,包括转录、翻译和mRNA降解。本项目的核心假设是:1)可以发现定量的sRNA结构/功能设计原则,并用于合理优化和扩展RNA调节因子的功能;2)可以发现电路级设计规则,并用于设计新的合成RNA遗传模块,控制基因表达的时间和模式。本CAREER项目的中心目标是使用小转录激活RNA (STARs)作为揭示合成生物学中RNA调节因子的定量设计原则的试验台。这将采用多方面的方法,包括使用尖端的RNA结构测量技术来阐明STARs的分子水平设计原则。一旦掌握了分子水平的原理,该项目将专注于使用这些技术来学习将STARs整合到决策监管网络中的设计规则。此外,新的实验和计算工具可以定量模拟由STARs介导的基因表达动力学,以了解STAR功能的不同方面如何通过RNA网络传播。这些研究的成功完成将推动更广泛的目标,即创建一个生物设计的定量学科,可用于编程细胞系统,以解决可持续能源和生物制造中的重要问题。此外,这项工作可能为自然发生的生物系统的天然小RNA调控机制提供见解。教育活动包括制定一项长期计划,继续冷泉港合成生物学暑期课程,作为全球范围内广泛的学生和教师的培训中心;为培养未来几代合成生物学家编写定量的课程材料;并针对有学龄儿童的家庭开展动手活动,让他们兴奋并了解合成生物学。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A primer on emerging field-deployable synthetic biology tools for global water quality monitoring
- DOI:10.1038/s41545-020-0064-8
- 发表时间:2020-04
- 期刊:
- 影响因子:11.4
- 作者:Walter Thavarajah;Matthew S. Verosloff;J. Jung;Khalid K. Alam;Joshua D. Miller;M. Jewett;S. Young;J. Lucks
- 通讯作者:Walter Thavarajah;Matthew S. Verosloff;J. Jung;Khalid K. Alam;Joshua D. Miller;M. Jewett;S. Young;J. Lucks
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Julius Lucks其他文献
Julius Lucks的其他文献
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{{ truncateString('Julius Lucks', 18)}}的其他基金
Transitions: Evolving our Understanding of Dynamic RNA Folding and Function
转变:加深我们对动态 RNA 折叠和功能的理解
- 批准号:
2310382 - 财政年份:2023
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
URoL:ASC: The design, development, and societal impact of rapid, in-home, water quality biosensors
URoL:ASC:快速家用水质生物传感器的设计、开发和社会影响
- 批准号:
2319427 - 财政年份:2023
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
NRT-URoL: Synthesizing Biology Across Scales – A Convergent Synthetic Biology Training Program
NRT-URoL:跨尺度合成生物学 — 融合合成生物学培训计划
- 批准号:
2021900 - 财政年份:2020
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
RAPID: Point-of-Need Detection of COVID-19 using CRISPR-Enabled Cell-Free Synthetic Biology
RAPID:使用支持 CRISPR 的无细胞合成生物学对 COVID-19 进行定点检测
- 批准号:
2028651 - 财政年份:2020
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
RAPID: Collaborative Research: A cell-free synthetic biology platform for water quality monitoring - field testing and validation at the Camp Fire site in Paradise, California
RAPID:协作研究:用于水质监测的无细胞合成生物学平台 - 在加利福尼亚州天堂市 Camp Fire 现场进行现场测试和验证
- 批准号:
1929912 - 财政年份:2019
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
Collaborative Research: Uncovering How Riboswitches Exploit Out-of-Equilibrium RNA Folding Pathways to Make Genetic Decisions
合作研究:揭示核糖开关如何利用非平衡 RNA 折叠途径做出遗传决策
- 批准号:
1914567 - 财政年份:2019
- 资助金额:
$ 57.41万 - 项目类别:
Continuing Grant
GOALI: Advanced biomanufacturing with inducible feedback promoters
目标:具有诱导反馈启动子的先进生物制造
- 批准号:
1803747 - 财政年份:2018
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
CAREER: Uncovering Quantitative Design Principles of RNA Regulators For Synthetic Biology
职业:揭示合成生物学 RNA 调节剂的定量设计原理
- 批准号:
1452441 - 财政年份:2015
- 资助金额:
$ 57.41万 - 项目类别:
Continuing Grant
The Nuts and Bolts of Bioengineered Systems: A Workshop on Standards in Synthetic Biology; Valencia, Spain- March 8-10, 2015
生物工程系统的具体细节:合成生物学标准研讨会;
- 批准号:
1523345 - 财政年份:2015
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
Dynamic Control of Glycan Biosynthesis with Synthetic RNA Circuitry
利用合成 RNA 电路动态控制聚糖生物合成
- 批准号:
1402843 - 财政年份:2014
- 资助金额:
$ 57.41万 - 项目类别:
Standard Grant
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