Collaborative Research: Booting up a Mirror Cell

地球上生命的一个标志是手性，或者说许多关键的生物分子--蛋白质、核酸、糖和脂--具有相同的手性。术语手性指的是对象与其镜像可区分的属性。我们通常将这一特性通俗地称为惯用手，因为我们的左手和右手不能重叠，而是彼此的镜像。这些性质推动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，通过它我们将从根本上了解生物分子、系统和过程中的手性。从应用的角度来看，这项工作可以生产出具有更好稳定性和活性的全新材料和镜面药物。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。这项提案还将促进跨学科教育，包括具体扩大STEM教育，并为代表不足的少数群体和妇女提供就业机会。为了教育公众，研究小组将邀请艺术界通过艺术来说明手性的科学，最终将在当地博物馆展出一场名为《镜子世界》的展览。通过这样做，研究团队的目标是向公众传达分子利手的重要性，确保这个项目取得的进展造福于更广泛的社区，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、构建和安全地部署合成镜像细胞，在这个细胞中，所有关键分子-核酸、蛋白质、碳水化合物和脂质-都以与其自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；预测含有镜像组件的细胞的生理；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，并在生物技术领域开辟新的应用。人工合成的镜像细胞将提供一种独特的透镜，帮助破译手性在生命多个尺度上的作用，并解释为什么自然生命专注于一种手性。研究人员将通过五项联合研究、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械来合成镜像核酸和蛋白质；(3)开发用于预测替代手性的生理影响的计算框架；(4)找出当前合成细胞的伦理、法律和环境框架中的漏洞，并提出评估镜像生命的风险和回报的新指标；以及(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，激励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、评估和安全部署在生物技术、医药和工业中具有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，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.