{"id":51178,"date":"2024-10-22T12:47:56","date_gmt":"2024-10-22T19:47:56","guid":{"rendered":"https:\/\/www.salk.edu\/?post_type=disclosure&#038;p=51178"},"modified":"2024-11-13T20:51:10","modified_gmt":"2024-11-14T04:51:10","slug":"through-the-looking-glass-a-cross-chiral-reaction-challenges-our-definition-of-life","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/through-the-looking-glass-a-cross-chiral-reaction-challenges-our-definition-of-life\/","title":{"rendered":"Through the looking glass: A cross-chiral reaction challenges our definition of life"},"content":{"rendered":"<p>LA JOLLA\u2014Just like your left and right hand exist as mirror images of each other, many biological molecules have their own form of left- and right-handedness, called chirality. Our DNA, for example, is made of right-handed chiral molecules which combine to form a right-handed double helix. The left-handed version would look like its mirror image, forming a helix that spins in the opposite direction.\r\n<\/p><p>\r\nThe thing about nature, though\u2014it tends to pick a side. On Earth, DNA and RNA exist only in their right-handed forms. Even when scientists construct synthetic left-handed versions of these molecules, the two groups behave as if on opposite sides of a mirror, unable to interact with each other.\r\n<\/p><p>\r\nBut what if they could? What if a molecule could reach through the mirror and interact with the reflected world on the other side? What if this set off a chain reaction that got molecules on both sides working together in ways we\u2019ve never seen before?\r\n<\/p>\r\n<figure id=\"attachment_51013\"  class=\"wp-caption alignright\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Cochrane-Bare-Joyce-Horning.png\"><img decoding=\"async\" class=\"img-responsive wp-image-51013 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Cochrane-Bare-Joyce-Horning-458x458.png\" alt=\"From top left: Wesley Cochrane and Grant Bare. From bottom left: David Horning and Gerald Joyce.\" \/><\/a><figcaption class=\"wp-caption-text\">From top left: Wesley Cochrane and Grant Bare. From bottom left: David Horning and Gerald Joyce.\r\n<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Cochrane-Bare-Joyce-Horning.png\" target=\"_blank\" rel=\"noopener\">Click here<\/a> for a high-resolution image.<br \/>Credit: Salk Institute<\/figcaption><\/figure>\r\n<p>\r\nThis is precisely what scientists at the Salk Institute have now achieved. In a study published on October 22, 2024, in <em><a href=\"https:\/\/www.pnas.org\/doi\/10.1073\/pnas.2413668121\" rel=\"noopener\" target=\"_blank\">Proceedings of the National Academy of Sciences<\/a><\/em>, the researchers demonstrate the first cross-chiral exponential amplification of an RNA enzyme. Using sophisticated bioengineering techniques, they produced a chemical system in which left- and right-handed versions of an RNA enzyme can effectively \u201creach through the mirror\u201d and replicate each other. Through this cross-chiral self-replication, the amount of both molecules increases exponentially and indefinitely\u2014something rarely seen outside of biology.\r\n<\/p><p>\r\nIn fact, NASA defines life as \"a self-sustaining chemical system capable of Darwinian evolution.\" The researchers say this is the first evidence of a life-like chemical system that operates on both sides of the mirror of chirality.\r\n<\/p><p>\r\n\u201cExponential self-replication is necessary for growth and evolution in every living system,\u201d says co-corresponding author and Salk President <a href=\"https:\/\/www.salk.edu\/zh\/scientist\/gerald-joyce\/\" rel=\"noopener\" target=\"_blank\">Gerald Joyce<\/a>. \u201cCells don\u2019t just make more of themselves; they make exponentially more of themselves, and that fast growth is what drives competition, natural selection, and evolution. We\u2019ve now shown that we can engineer forms of exponential genetic self-replication that are not yet life but are on the path to it, and are built on interactions between left- and right-handed molecules.\u201d\r\n<\/p><p>\r\nWhile cross-chiral self-replication is unlikely to occur spontaneously in nature, the discovery that it can be engineered in a laboratory setting suggests scientists could one day synthesize an artificial living system that uses both left- and right-handed molecules. This would create the opportunity to study an entirely new form of biochemical evolution, and could also lead to the development of cross-chiral therapeutics and biotechnologies.\r\n<\/p>\r\n<figure id=\"attachment_51013\"  class=\"wp-caption alignleft\"><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Joyce-Horning-PNAS.png\"><img decoding=\"async\" class=\"img-responsive wp-image-51013 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Joyce-Horning-PNAS-300x427.png\" alt=\"Salk scientists engineered a right-handed RNA enzyme (bottom left) that can combine left-handed RNA fragments (bottom right) to create a mirror image of itself. The new left-handed RNA enzyme (top right) can then combine right-handed RNA fragments (top left) to produce more of the original right-handed enzyme, restarting the cycle of cross-chiral self-replication. Adapted from Cochrane et al., PNAS 2024.\" \/><\/a><figcaption class=\"wp-caption-text\">Salk scientists engineered a right-handed RNA enzyme (bottom left) that can combine left-handed RNA fragments (bottom right) to create a mirror image of itself. The new left-handed RNA enzyme (top right) can then combine right-handed RNA fragments (top left) to produce more of the original right-handed enzyme, restarting the cycle of cross-chiral self-replication. Adapted from Cochrane et al., PNAS 2024.\r\n<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2024\/10\/Joyce-Horning-PNAS.png\" target=\"_blank\" rel=\"noopener\">Click here<\/a> for a high-resolution image.<br \/>Credit: Salk Institute<\/figcaption><\/figure>\r\n<p>\r\n\u201cWe\u2019ve come to expect that life on our planet and other planets will be single-handed, but our work suggests that doesn\u2019t have to be true for a bioengineer,\u201d says co-corresponding author David Horning, a senior staff scientist in Joyce\u2019s lab. \u201cWe\u2019re essentially exploring the boundaries of what biology can be, and based on this study, it seems that our definition of life doesn\u2019t have to be as narrow in the lab as it is in nature.\u201d\r\n<\/p><p>\r\nTo achieve cross-chiral exponential amplification, co-first authors Wesley Cochrane and Grant Bare expanded on the lab\u2019s pioneering methods for driving the directed evolution of RNAs. In this case, the system was used to produce an RNA enzyme that is very good at making the opposite-handed version of itself. Importantly, the same enzyme could now be further engineered to also make additional RNA products that carry out other valuable functions. The resulting cross-chiral autocatalytic system could have many applications in medicine and biomanufacturing.\r\n<\/p><p>\r\nFor example, the authors say they could one day synthesize new left-handed RNAs that interact with right-handed molecules in the body in very specific, desired ways. Because these left-handed RNAs would go virtually undetected by the cell and immune system, they wouldn\u2019t degrade as quickly as other drugs. They also wouldn\u2019t be able to interact with any other right-handed molecules, reducing the likelihood of off-target side effects.\r\n<\/p><p>\r\nThis cross-chiral strategy could inspire an entirely new class of therapeutics, diagnostics, and research tools. The Joyce lab has already developed systems to produce left-handed RNAs that bind to disease-related RNAs and proteins. Another project is exploring their use as signal amplifiers, allowing researchers and clinicians to detect trace amounts of specific molecules of interest, such as viral RNAs.\r\n<\/p><p>\r\n\u201cIt\u2019s like having a parallel biology that exists next to our biology, but it\u2019s designed entirely by us and nature can\u2019t interfere with it,\u201d says Horning. \u201cCross-chiral self-replication opens up a whole new world of biochemical possibilities, so we\u2019re just beginning to imagine all of the ways we could use these mirrored molecules to our benefit.\u201d\r\n<\/p><p>\r\nThe work was supported by the National Science Foundation (MCB2114588) in collaboration with Professor Jon Sczepanski at Texas A&M University and the National Institutes of Health Ruth L. Kirschstein National Research Service Award (F32GM146435) to Wesley Cochrane.\r\n<\/p>","protected":false},"featured_media":51520,"template":"","faculty":[309],"disease-research":[449],"class_list":["post-51178","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-gerald-joyce","disease-research-biochemistry-and-biophysics"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Through the looking glass: A cross-chiral reaction challenges our definition of life - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/through-the-looking-glass-a-cross-chiral-reaction-challenges-our-definition-of-life\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Through the looking glass: A cross-chiral reaction challenges our definition of life - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Just like your left and right hand exist as mirror images of each other, many biological molecules have their own form of left- and right-handedness, called chirality. 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