ABSTRACT

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.

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