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Collaborative Research: Booting up a Mirror Cell

合作研究：启动镜像单元

基本信息

批准号：
1935120
负责人：
Farren Isaacs
金额：
$ 118.6万
依托单位：
Yale University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935120&HistoricalAwards=false
关键词：
Collaborative Research Booting up Mirror

项目摘要

A hallmark of life on Earth is homochirality, or the fact that many of the key biological molecules - proteins, nucleic acids, sugars, and lipids - possess the same chirality. The term chirality refers to the property of an object to be distinguishable from its mirror image. We often refer to this property colloquially as handedness, as our left and right hands are not superimposable yet are mirror images of one another. These properties motivate the exploration of constructing and studying mirror biomolecules. In this project, the researchers seek to take the first steps toward building a mirror synthetic cell, providing a unique lens through which we will attain a fundamental understanding of chirality in biological molecules, systems, and processes. From an applied perspective, the work could enable production of entirely new classes of materials and mirror drugs endowed with improved stability and activity. Creating substances that were previously impossible to create will lead to the next-generation of renewable biotechnology and medical products. This proposal will also promote interdisciplinary education, including the specific expansion of STEM education and career opportunities for underrepresented minorities and women. To educate the public, the research team will engage the artistic community to illustrate the science of chirality through art, culminating in a 'Mirror World' exhibit that will be displayed at local museums. By doing so, the research team aim to communicate the importance of molecular handedness to the public, ensuring that advances made in this project benefit a broader community and contribute to inspiring and training young scientists and engineers.In this project, the researchers seek to design, construct, and safely deploy synthetic mirror cells in which all of the key molecules - nucleic acids, proteins, carbohydrates, and lipids - exist in chiral states opposite to their natural forms. Toward this goal, the team will develop the capabilities to synthesize mirror DNA, RNA, and proteins; predict the physiology of cells with mirror components; and assess the risks and rewards of mirror life. If successful, this project will transform basic science, bioengineering, and open up new applications in biotechnology. Synthetic mirror cells will offer a unique lens to help decipher the role of chirality across multiple scales of life and elucidate why natural life has focused on one chirality. The researchers will develop a foundation for mirror cells via five coupled research, education, and outreach activities: (1) developing schemes for chemically synthesizing mirror biomolecules; (2) repurposing the natural biological machinery to synthesize mirror nucleic acids and proteins; (3) developing a computational framework for predicting the physiological impact of alternative chirality; (4) identifying gaps in the current ethical, legal, and environmental framework for synthetic cells and proposing new metrics for assessing the risks and rewards of mirror life; and (5) inspiring and educating the public about the potential of mirror life by working with artists to develop a museum exhibit titled 'The Mirror World.' Looking forward, this work will be a foundation for the know-how and capabilities to design, produce, evaluate, and safely deploy synthetic mirror cells with transformative potential in biotechnology, medicine, and industry.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.

地球上生命的一个标志是同手性，或者说许多关键的生物分子--蛋白质、核酸、糖和脂质--都具有相同的手性。术语手征性是指物体与其镜像可区分的性质。我们通常将这种特性通俗地称为利手性，因为我们的左手和右手是不可重叠的，但它们是彼此的镜像。这些性质激发了构建和研究镜像生物分子的探索。在这个项目中，研究人员试图迈出建立镜像合成细胞的第一步，提供一个独特的透镜，通过它我们将获得对生物分子，系统和过程中手性的基本理解。从应用的角度来看，这项工作可以使生产具有改进的稳定性和活性的全新类型的材料和镜像药物成为可能。创造以前不可能创造的物质将导致下一代可再生生物技术和医疗产品。该提案还将促进跨学科教育，包括为代表性不足的少数民族和妇女具体扩大STEM教育和职业机会。为了教育公众，研究团队将邀请艺术界通过艺术来说明手性科学，最终将在当地博物馆展出的“镜像世界”展览中达到高潮。通过这样做，研究团队旨在向公众传达分子手性的重要性，确保该项目的进展使更广泛的社区受益，并有助于激励和培训年轻的科学家和工程师。在这个项目中，研究人员寻求设计，构建和安全部署合成镜像细胞，其中所有关键分子-核酸，蛋白质，碳水化合物，和脂质-以与其天然形式相反的手性状态存在。为了实现这一目标，该团队将开发合成镜像DNA、RNA和蛋白质的能力;预测具有镜像成分的细胞的生理学;并评估镜像生命的风险和回报。如果成功，该项目将改变基础科学，生物工程，并开辟生物技术的新应用。合成镜细胞将提供一个独特的透镜，帮助破译手性在生命的多个尺度上的作用，并阐明为什么自然生命集中在一个手性上。研究人员将通过五个耦合的研究，教育和推广活动为镜像细胞奠定基础：（1）开发化学合成镜像生物分子的方案;（2）重新利用自然生物机制合成镜像核酸和蛋白质;（3）开发预测替代手性的生理影响的计算框架;（4）开发一个新的计算框架。（4）找出目前合成细胞的伦理、法律的和环境框架中的差距，并提出评估镜像生命的风险和回报的新指标;（5）通过与艺术家合作开发一个名为"镜像世界"的博物馆展览，激发和教育公众关于镜像生命的潜力。"展望未来，这项工作将成为设计、生产、评估和安全部署具有生物技术、医学和工业变革潜力的合成镜像细胞的技术和能力的基础。该奖项反映了NSF的法定使命，并被认为值得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来支持。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Making Security Viral: Shifting Engineering Biology Culture and Publishing

让安全病毒式传播：改变工程生物学文化和出版

DOI：
10.1021/acssynbio.1c00324
发表时间：
2022
期刊：
ACS Synthetic Biology
影响因子：
4.7
作者：
Mackelprang, Rebecca;Adamala, Katarzyna P.;Aurand, Emily R.;Diggans, James C.;Ellington, Andrew D.;Evans, Samuel Weiss;Fortman, J. L.;Hillson, Nathan J.;Hinman, Albert W.;Isaacs, Farren J.
通讯作者：
Isaacs, Farren J.

Targeted editing and evolution of engineered ribosomes in vivo by filtered editing.