Engineering of next-generation synthetic biology tools for biological applications

用于生物应用的下一代合成生物学工具的工程

基本信息

  • 批准号:
    RGPIN-2019-07002
  • 负责人:
  • 金额:
    $ 2.7万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2020
  • 资助国家:
    加拿大
  • 起止时间:
    2020-01-01 至 2021-12-31
  • 项目状态:
    已结题

项目摘要

Synthetic biology, by engineering biological systems for specific functions, could address many societal needs, whether in medicine, in environmental remediation, or in the green production of chemicals. However, foundational work remains to be done before synthetic biology can effectively address these challenges. For example, while synthetic circuits made of well-characterized components have been able to achieve a variety of functions, they generally have done so at a much lower precision, robustness, and stability than their natural counterparts. The long-term goals of my research program are to engineer next-generation synthetic gene circuits suitable for impactful applications, and to use them as models and tools to learn more about biology. Recently, we succeeded in engineering by far the most precise and robust synthetic circuit to date. This was achieved by using a quantitative approach and a microfluidic device enabling precise characterization of the dynamics of thousands of individual bacteria for hundreds of generations under precisely controlled growth conditions. However, this precision required expressing high number of proteins, which can impose a metabolic burden on the cells by using up scarce cellular resources. Such burden has made previous synthetic circuits unusable in industrial contexts, because natural selection immediately breaks such circuits. In this research proposal, we will generalize our previous approach to generate a wide range of synthetic oscillators with specific properties (toolbox of oscillators, Obj. 1): precision, robustness, period, amplitude, metabolic burden, etc. The number of these circuits and the range of their specific properties will be orders of magnitude greater than the few synthetic oscillators currently available. These toolboxes will enable us to study how cells can encode information in the dynamics of their protein levels and enable applications such as dynamic drug delivery (i.e. temporal variation of the level of drugs). We will also add new parts to the synthetic biologist toolkit, by measuring the memory properties of prion proteins in order to develop them as ultra-stable synthetic memory elements (Obj. 2). Prion proteins have recently been found to have a functional role across domains of life as a form of non-genetic inheritance, and measuring their dynamic properties in our microfluidic device will enable us to test hypotheses about the currently unknown mechanisms of prion formation and loss. Finally, we will use a recently developed burden sensor to optimize our synthetic circuits to be precise while carrying a low burden on their cellular host (Obj. 3), opening up their use in impactful applications. These objectives represent the first step towards our long-term goals, by providing the foundation for technologies such as dynamical drug delivery while teaching us about biology, for example by understanding mechanisms of prion-based information transfer.
合成生物学通过设计用于特定功能的生物系统,可以满足许多社会需求,无论是在医学、环境补救或绿色化学品生产方面。然而,在合成生物学能够有效地应对这些挑战之前,仍需进行基础性工作。例如,虽然由特性良好的元件制成的合成电路能够实现各种功能,但它们通常以比天然电路低得多的精度、健壮性和稳定性来实现。我的研究计划的长期目标是设计适合于有效应用的下一代合成基因电路,并将它们用作学习更多生物学知识的模型和工具。 最近,我们成功地设计出了迄今为止最精确和最坚固的合成电路。这是通过使用定量方法和微流控装置实现的,该装置能够在精确受控的生长条件下精确描述数百代数千种单个细菌的动态。然而,这种精确度需要表达大量的蛋白质,这可能会通过耗尽稀缺的细胞资源而对细胞施加新陈代谢负担。这样的负担使以前的合成电路在工业环境中无法使用,因为自然选择会立即破坏这种电路。在这项研究提案中,我们将推广我们以前的方法来生成一系列具有特定性质的合成振荡器(OBJ.1):精度、稳健性、周期、幅度、代谢负荷等。这些电路的数量及其特性的范围将比目前可用的少数几个合成振荡器大几个数量级。这些工具箱将使我们能够研究细胞如何在其蛋白质水平的动态中编码信息,并使诸如动态药物输送(即药物水平的时间变化)等应用成为可能。我们还将在合成生物学家工具包中添加新的部分,通过测量Pron蛋白的记忆属性,以便将它们开发为超稳定的合成记忆元件(Obj。2)。最近发现Pron蛋白作为一种非遗传遗传形式在生命的各个领域具有功能作用,在我们的微流控设备中测量它们的动态性质将使我们能够测试关于目前未知的Pron形成和丢失机制的假说。最后,我们将使用最近开发的负载传感器来优化我们的合成电路,使其在精确的同时对其蜂窝宿主(OBJ。3),开放它们在有影响力的应用中的使用。这些目标代表着我们迈向长期目标的第一步,通过为动态药物输送等技术提供基础,同时向我们传授生物学知识,例如通过了解基于Pron的信息传输机制。

项目成果

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PotvinTrottier, Laurent其他文献

PotvinTrottier, Laurent的其他文献

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{{ truncateString('PotvinTrottier, Laurent', 18)}}的其他基金

Engineering of next-generation synthetic biology tools for biological applications
用于生物应用的下一代合成生物学工具的工程
  • 批准号:
    RGPIN-2019-07002
  • 财政年份:
    2022
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Grants Program - Individual
Engineering of next-generation synthetic biology tools for biological applications
用于生物应用的下一代合成生物学工具的工程
  • 批准号:
    RGPIN-2019-07002
  • 财政年份:
    2021
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Grants Program - Individual
Engineering of next-generation synthetic biology tools for biological applications
用于生物应用的下一代合成生物学工具的工程
  • 批准号:
    DGECR-2019-00357
  • 财政年份:
    2019
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Launch Supplement
Engineering of next-generation synthetic biology tools for biological applications
用于生物应用的下一代合成生物学工具的工程
  • 批准号:
    RGPIN-2019-07002
  • 财政年份:
    2019
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Discovery Grants Program - Individual
Investigation of plasmids copy number temporal dynamics in single bacterial cells
单细菌细胞中质粒拷贝数时间动态的研究
  • 批准号:
    454307-2014
  • 财政年份:
    2015
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Investigation of plasmids copy number temporal dynamics in single bacterial cells
单细菌细胞中质粒拷贝数时间动态的研究
  • 批准号:
    454307-2014
  • 财政年份:
    2014
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Postgraduate Scholarships - Doctoral
Mapping Forces and Molecular Transport Simultaneously in Living Cells
同时绘制活细胞中的力和分子运输
  • 批准号:
    408968-2011
  • 财政年份:
    2011
  • 资助金额:
    $ 2.7万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Mapping protein transport in cells and neurons using spatio-temporal image correlation
使用时空图像相关性绘制细胞和神经元中的蛋白质运输图
  • 批准号:
    398696-2010
  • 财政年份:
    2010
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards
Etude de la fluoresence des points quantiques fabriqués par laser
激光量子点荧光练习
  • 批准号:
    366089-2008
  • 财政年份:
    2008
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards
Caractérisation de résistances en silicium polycristallin modifiées par laser
激光改性硅多晶电阻的表征
  • 批准号:
    353331-2007
  • 财政年份:
    2007
  • 资助金额:
    $ 2.7万
  • 项目类别:
    University Undergraduate Student Research Awards

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