{"id":1859,"date":"2018-09-25T13:51:10","date_gmt":"2018-09-25T04:51:10","guid":{"rendered":"http:\/\/163.180.4.222\/lab\/?p=1859"},"modified":"2018-09-25T13:51:10","modified_gmt":"2018-09-25T04:51:10","slug":"programmable-protein-circuits-in-living-cells","status":"publish","type":"post","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1859","title":{"rendered":"Programmable protein circuits in living cells"},"content":{"rendered":"<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p><cite>Science\u00a0<\/cite>\u00a021 Sep 2018:<br \/>\nVol. 361, Issue 6408, pp. 1252-1258<br \/>\nDOI: 10.1126\/science.aat5062<\/p>\n<p>&nbsp;<\/p>\n<p><a href=\"http:\/\/science.sciencemag.org\/content\/361\/6408\/1252?rss=1\"><u>\uc5ec\uae30<\/u><\/a>\ub97c \ud074\ub9ad\ud558\uc138\uc694~<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h6>Building smarter synthetic biological circuits<\/h6>\n<p id=\"p-3\">Synthetic genetic and biological regulatory circuits can enable logic functions to form the basis of biological computing; synthetic biology can also be used to control cell behaviors (see the Perspective by Glass and Alon). Andrews\u00a0<em>et al.<\/em>\u00a0used mathematical models and computer algorithms to combine standardized components and build programmable genetic sequential logic circuits. Such circuits can perform regulatory functions much like the biological checkpoint circuits of living cells. Circuits composed of interacting proteins could be used to bypass gene regulation, interfacing directly with cellular pathways without genome modification. Gao\u00a0<em>et al.<\/em>\u00a0engineered proteases that regulate one another, respond to diverse inputs that include oncogene activation, process signals, and conditionally activate responses such as those leading to cell death. This platform should facilitate development of \u201csmart\u201d therapeutic circuits for future biomedical applications.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<h6>Abstract<\/h6>\n<p id=\"p-6\">Synthetic protein-level circuits could enable engineering of powerful new cellular behaviors. Rational protein circuit design would be facilitated by a composable protein-protein regulation system in which individual protein components can regulate one another to create a variety of different circuit architectures. In this study, we show that engineered viral proteases can function as composable protein components, which can together implement a broad variety of circuit-level functions in mammalian cells. In this system, termed CHOMP (circuits of hacked orthogonal modular proteases), input proteases dock with and cleave target proteases to inhibit their function. These components can be connected to generate regulatory cascades, binary logic gates, and dynamic analog signal-processing functions. To demonstrate the utility of this system, we rationally designed a circuit that induces cell death in response to upstream activators of the Ras oncogene. Because CHOMP circuits can perform complex functions yet be encoded as single transcripts and delivered without genomic integration, they offer a scalable platform to facilitate protein circuit engineering for biotechnological applications.<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>&nbsp; &nbsp; Science\u00a0\u00a021 Sep 2018: Vol. 361, Issue 6408, pp. 1252-1258 DOI: 10.1126\/science.aat5062 &nbsp; \uc5ec\uae30\ub97c \ud074\ub9ad\ud558\uc138\uc694~ &nbsp; &nbsp; Building smarter synthetic biological circuits Synthetic genetic<a href=\"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1859\" class=\"more-link\">(more&#8230;)<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[33,29,30],"tags":[],"class_list":["post-1859","post","type-post","status-publish","format-standard","hentry","category-do-biology","category-lets-do-science","category-recent-science-news"],"aioseo_notices":[],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack-related-posts":[{"id":3495,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=3495","url_meta":{"origin":1859,"position":0},"title":"Cooperativity in synthetic gene circuits","author":"biochemistry","date":"May 10, 2019","format":false,"excerpt":"\u00a0 \u00a0 Synthetic biologists would like to be able to make gene regulatory circuits that mimic key properties of eukaryotic gene regulation. Taking a cue from multimeric transcription factor complexes, Bashor\u00a0et al.\u00a0developed synthetic transcriptional circuits that produce nonlinear behavior from cooperativity (see the Perspective by Ng and El-Samad). Their system\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4881,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4881","url_meta":{"origin":1859,"position":1},"title":"Interfacing electronic and genetic circuits","author":"biochemistry","date":"December 14, 2019","format":false,"excerpt":"\u00a0 \u00a0 Synthetic genetic circuits leverage the information processing capability of biological machinery to tackle complex sensing tasks, yet they lack many of the advantages inherent to electrical computation. Now, an interface has been designed that provides an electrical output for synthetic genetic circuits. \u00a0 \u00a0 Synthetic genetic circuits are\u2026","rel":"","context":"In &quot;Let's Do Chemistry!&quot;","block_context":{"text":"Let's Do Chemistry!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=34"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1126,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1126","url_meta":{"origin":1859,"position":2},"title":"Engineering multilayered cellular structures","author":"biochemistry","date":"July 17, 2018","format":false,"excerpt":"\u00a0 \u00a0 (\uc6d0\ubb38: \uc5ec\uae30\ub97c \ud074\ub9ad\ud558\uc138\uc694~) \u00a0 \u00a0 Science\u00a0\u00a013 Jul 2018: Vol. 361, Issue 6398, pp. 141-143 DOI: 10.1126\/science.361.6398.141-k \u00a0 \u00a0 \u00a0 The ability to program the manufacture of biological structures may yield new biomaterials or synthetic tissues and organs. Toda\u00a0et al.\u00a0engineered mammalian \u201csender\u201d and \u201creceiver\u201d cells with synthetic cell surface\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":2795,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=2795","url_meta":{"origin":1859,"position":3},"title":"DNA-based communication in populations of synthetic protocells","author":"biochemistry","date":"March 7, 2019","format":false,"excerpt":"\u00a0 \u00a0 Abstract \u00a0 Developing molecular communication platforms based on orthogonal communication channels is a crucial step towards engineering artificial multicellular systems. Here, we present a general and scalable platform entitled \u2018biomolecular implementation of protocellular communication\u2019 (BIO-PC) to engineer distributed multichannel molecular communication between populations of non-lipid semipermeable microcapsules. Our\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":4114,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=4114","url_meta":{"origin":1859,"position":4},"title":"Glowing DNA label illuminates a cell\u2019s fine details","author":"biochemistry","date":"September 23, 2019","format":false,"excerpt":"\u00a0 \u00a0 Fluorescent tag can be affixed to proteins or genetic structures of interest. \u00a0 \u00a0 DNA tags could help scientists to study ion channels (yellow), which allow specific ions to pass through the membrane of nerve cells (green). Credit: Patrick Landmann\/SPL \u00a0 \u00a0 \u00a0 A glowing tag made of\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1975,"url":"https:\/\/biochemistry.khu.ac.kr\/lab\/?p=1975","url_meta":{"origin":1859,"position":5},"title":"Intracellular gold nanoclusters boost energy conversion","author":"biochemistry","date":"October 2, 2018","format":false,"excerpt":"\u00a0 \u00a0 \uc0c8\ub85c\uc6b4 \ud615\ud0dc\uc758 '\ubc15\ud14c\ub9ac\uc544 \uc138\ud3ec \ub0b4\ubd80\ub85c \ub3c4\uc785\ub41c \uae08 \ub098\ub178\ubb3c\uc9c8 \uae30\ubc18 \uc5d0\ub108\uc9c0 \uc804\ud658 \uc2dc\uc2a4\ud15c'\uc5d0 \uad00\ud55c \ub0b4\uc6a9\uc785\ub2c8\ub2e4. (\uc6d0\ubb38: \uc5ec\uae30\ub97c \ud074\ub9ad\ud558\uc138\uc694~) \u00a0 Intracellular gold nanoclusters act as photosensitizers, enabling non-photosynthetic bacteria to produce acetic acid from carbon dioxide in a more efficient and durable fashion. \u00a0 \u00a0 Driven by ever-growing consumption, humankind\u2026","rel":"","context":"In &quot;Let's Do Biology!&quot;","block_context":{"text":"Let's Do Biology!","link":"https:\/\/biochemistry.khu.ac.kr\/lab\/?cat=33"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]}],"jetpack_sharing_enabled":false,"jetpack_shortlink":"https:\/\/wp.me\/p9Xo1j-tZ","_links":{"self":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1859","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1859"}],"version-history":[{"count":1,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1859\/revisions"}],"predecessor-version":[{"id":1860,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=\/wp\/v2\/posts\/1859\/revisions\/1860"}],"wp:attachment":[{"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1859"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1859"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biochemistry.khu.ac.kr\/lab\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1859"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}