{"id":15466,"date":"2019-03-28T20:00:55","date_gmt":"2019-03-28T19:00:55","guid":{"rendered":"https:\/\/news.embl.de\/?p=15466"},"modified":"2024-03-22T11:19:23","modified_gmt":"2024-03-22T10:19:23","slug":"new-functionalities-for-cells","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/new-functionalities-for-cells\/","title":{"rendered":"Designer organelles bring new functionalities into cells"},"content":{"rendered":"\n<p>For the first time, scientists have engineered the complex biological process of translation into a designer organelle in a living mammalian cell. Research by the <a href=\"https:\/\/www.embl.de\/research\/units\/scb\/lemke\/index.html\" target=\"_blank\" rel=\"noopener noreferrer\">Lemke group<\/a> at the European Molecular Biology Laboratory (EMBL) \u2013 in collaboration with JGU Mainz and IMB Mainz \u2013 used this technique to create a membraneless organelle that can build proteins from natural and synthetic amino acids carrying new functionality. Their results \u2013 published in <em>Science<\/em> on 29 March \u2013 allow scientists to study, tailor, and control cellular function in more detail.<\/p>\n\n\n<div\n  class=\"vf-embed vf-embed--custom-ratio\"\n\n  style=\"--vf-embed-max-width: 100%;\n    --vf-embed-custom-ratio-x: 640;\n    --vf-embed-custom-ratio-y: 360;\"><iframe loading=\"lazy\" width=\"640\" height=\"360\" src=\"https:\/\/www.youtube.com\/embed\/d9O3N3IQ3yc\" frameborder=\"0\" allow=\"accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe><\/div>\n\n\n\n<p>During evolution, the development of new organelles allows cells and organisms to become more complex, due to the ability to sort cellular processes into specific hotspots. \u201cOur tool can be used to engineer translation, but potentially also other cellular processes like transcription and post-translational modifications. This might even allow us to engineer new types of organelles that extend the functional repertoire of natural complex living systems,\u201d explains Christopher Reinkemeier, PhD student at EMBL and JGU Mainz and co-first author of the paper. \u201cWe could for example incorporate fluorescent building blocks that allow a glimpse inside the cell using imaging methods.\u201d<\/p>\n\n\n\n<p>\u201cThe organelle can make proteins by using synthetic non-canonical amino acids. Currently we know of more than 300 different non-canonical amino acids \u2013 compared to 20 which are naturally occurring. We are no longer restricted to the latter ones,\u201d says co-first author Gemma Estrada Girona. \u201cThe novelty we introduce is the ability to use these in a confined space, the organelle, which minimises the effects on the host.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Wobbly wall-less organelles<\/h2>\n\n\n\n<p>Translation is such a complex process that it cannot be contained in one single organelle surrounded by a membrane. Therefore, inspiration was drawn from phase separation: the process responsible for the formation of membraneless organelles in vivo, such as nucleoli or stress granules. Phase separation is used by cells to locally concentrate specific proteins and RNAs. Even though these wall-less organelles have wobbly boundaries as they dynamically interact with the surrounding cytoplasm, they can still do very precise tasks. The team combines phase separation with cellular targeting to create their membraneless organelle and to make sure that only one organelle per cell is formed.<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image\"><a href=\"https:\/\/www.embl.de\/aboutus\/communication_outreach\/media_relations\/2019\/190329_Lemke_Science\/how-translation-works_l.png\" target=\"_blank\" rel=\"noreferrer noopener\"><img decoding=\"async\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.de\/aboutus\/communication_outreach\/media_relations\/2019\/190329_Lemke_Science\/how-translation-works_s.png\" alt=\"infographic about how translation works\"\/><\/a><figcaption class=\"vf-figure__caption\">The genetic code is made up of three-letter sequences called codons. Each one codes for an amino acid, except for three &#8216;stop&#8217; codons, which signal that an amino acid chain is complete. The Lemke group were able to develop a cell organelle that uses a reprogrammed stop codon, so that it codes for a new amino acid &#8211; not one of the 20 that occur naturally in living organisms.<br \/>IMAGE: Aleks Krolik\/EMBL<\/figcaption><\/figure>\n\n\n\n<p>In the end, only five new components have to be engineered into a cell to build it. The assembly of these components generates a large structure, which might create some burden on the cell. In the future, the group aims to engineer minimal designer organelles, to minimise any impact on the physiology of the healthy organism.<\/p>\n\n\n\n<p>Edward Lemke \u2013 visiting group Leader at EMBL, Professor at JGU Mainz and Adjunct Director at the IMB \u2013 led the project. He concludes: \u201cIn the end, we aim to develop a technique to engineer synthetic cellular organelles and proteins that do not affect the host machinery at all. We want to create a tool that does not have any uncharacterised effects. The organelle should be a simple add-on that allows organisms to do custom-designed novel things in a controlled fashion.\u201d<\/p>\n\n\n<hr class=\"vf-divider\"\/>\n\n\n\n<h2 class=\"wp-block-heading\" id=\"a1\">Designer-Organellen in Zellen stellen k\u00fcnstliche Proteine her<\/h2>\n\n\n\n<p>Forscherteam erzeugt membranlose Organellen in lebender Zelle f\u00fcr die Proteinsynthese \u2013 Einbau von synthetischen Aminos\u00e4uren erm\u00f6glicht komplett neue chemische Funktionalit\u00e4t<\/p>\n\n\n<div\n  class=\"vf-embed vf-embed--custom-ratio\"\n\n  style=\"--vf-embed-max-width: 100%;\n    --vf-embed-custom-ratio-x: 640;\n    --vf-embed-custom-ratio-y: 360;\"><iframe loading=\"lazy\" width=\"640\" height=\"360\" src=\"https:\/\/www.youtube.com\/embed\/d9O3N3IQ3yc\" frameborder=\"0\" allow=\"accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture\" allowfullscreen><\/iframe><\/div>\n\n\n\n<p>Einem Forscherteam um den biophysikalischen Chemiker Prof. Dr. Edward Lemke ist es gelungen, eine membranlose Organelle in einer lebenden Zelle zu erzeugen und damit selektiv Proteine herzustellen, in die synthetische Aminos\u00e4uren eingebaut sind. \u00dcber diese chemisch erzeugten Aminos\u00e4uren ist es m\u00f6glich, die Zellen mit v\u00f6llig neuen Funktionen auszustatten. Beispielsweise k\u00f6nnten fluoreszierende Bausteine eingebaut werden, die mit bildgebenden Verfahren einen Blick ins Innere der Zelle erlauben. Die Forschungsarbeit der Gruppe ist in Zusammenarbeit der Johannes Gutenberg-Universit\u00e4t Mainz (JGU), dem Institut f\u00fcr Molekulare Biologie (IMB) und dem European Molecular Biology Laboratory (EMBL) erfolgt und wurde in dem renommierten Wissenschaftsmagazin&nbsp;<em>Science<\/em>&nbsp;ver\u00f6ffentlicht.<\/p>\n\n\n\n<p><br \/>Organellen sind Kompartimente in Zellen, die wie der Kern oder die Mitochondrien bestimmte Funktionen erf\u00fcllen. Die Gruppe um Lemke hat nun ein neues Kompartiment erzeugt, in dem spezielle Proteine synthetisiert werden k\u00f6nnen. \u201eBildlich gesprochen suchen wir uns eine Ecke in der Zelle aus, wo wir unser Haus bauen und holen dann einen Teil der Ribosomen, die in der Zelle vorhanden sind, herein\u201c, beschreibt Edward Lemke das Vorgehen. An den Ribosomen erfolgt die Biosynthese von Proteinen. \u00dcber den genetischen Code wird dabei die Boten-RNA (mRNA) in die Abfolge der Aminos\u00e4uren f\u00fcr das neu zu bildende Protein \u00fcbersetzt.<br \/><br \/>Beim Bau der Designer-Organelle hat sich das Team um Lemke vom Prinzip der Phasenseparation inspirieren lassen: Phasenseparation wird von der Zelle verwendet, um spezielle Proteine und RNA lokal zu konzentrieren und neue, membranlose Kompartimente zu bauen. \u201eUnsere membranlose Organelle ist quasi ein offenes Reaktionszentrum\u201c, so Lemke.<br \/><br \/>Damit kann die Proteinbiosynthese an einem genau definierten Ort ablaufen, was f\u00fcr die Arbeit mit k\u00fcnstlichen Aminos\u00e4uren wichtig ist. Denn die Technik, mit Hilfe einer nicht nat\u00fcrlichen Aminos\u00e4ure ein neues Protein zu schaffen, ist bereits bekannt. Wenn dieser Einbau aber unspezifisch in der ganzen Zelle erfolgt, ist die Belastung gro\u00df und die Zelle wird unter Umst\u00e4nden stark beeintr\u00e4chtigt. Mit ihrer Methode der sogenannten orthogonalen Translation vermeiden die Wissenschaftler dieses Problem.<\/p>\n\n\n\n<h3 class=\"wp-block-heading\">Gro\u00dfer Fundus an nat\u00fcrlichen und synthetischen Aminos\u00e4uren f\u00fcr Proteinsynthese an Designer-Organellen<\/h3>\n\n\n\n<p>\u201eUnsere Organelle kann Proteine erzeugen, indem sie synthetisch hergestellte nicht-kanonische Aminos\u00e4uren verwendet. Davon gibt es zurzeit \u00fcber 300. Das hei\u00dft es gibt nun keine Beschr\u00e4nkungen mehr, nur die 20 kanonischen Aminos\u00e4uren zu nutzen\u201c, erkl\u00e4rt Gemma Estrada Girona, zusammen mit Christopher Reinkemeier Erstautorin der Science-Ver\u00f6ffentlichung. Beim Menschen bestehen die Proteine aus 20 nat\u00fcrlich vorkommende Aminos\u00e4uren, auch kanonische Aminos\u00e4uren genannt. Dar\u00fcber hinaus gibt es nicht-kanonische Aminos\u00e4uren, die nicht in normalen menschlichen Proteinen vorkommen. Die Erweiterung des genetischen Codes erm\u00f6glicht es, dass auch nicht-kanonische Aminos\u00e4uren eingebaut werden. Die neue Designer-Organelle ist in der Lage, den genetischen Code selektiv zu erweitern. Dadurch wird innerhalb der Organelle die RNA anders \u00fcbersetzt als im Rest der Zelle. \u201eWir haben uns die Natur zum Vorbild genommen, speziell den membranlosen Nukleolus, der im Zellkern an der Synthese von RNA beteiligt ist\u201c, erkl\u00e4rt Lemke. \u201eWir waren dann aber doch \u00fcberrascht, dass wir eine so komplizierte Struktur und Funktion tats\u00e4chlich mit wenigen Schritten selber bauen k\u00f6nnen.\u201c<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image\"><a href=\"https:\/\/www.embl.de\/aboutus\/communication_outreach\/media_relations\/2019\/190329_Lemke_Science\/how-translation-works_l.png\" target=\"_blank\" rel=\"noreferrer noopener\"><img decoding=\"async\" class=\"vf-figure__image\" src=\"https:\/\/www.embl.de\/aboutus\/communication_outreach\/media_relations\/2019\/190329_Lemke_Science\/how-translation-works_s.png\" alt=\"infographic about how translation works\"\/><\/a><figcaption class=\"vf-figure__caption\"><em>Der genetische Code besteht aus einer Sequenz von drei aufeinanderfolgenden Nukleobasen (Adenin, Guanin, Cytosin, Thymin) der Nukleins\u00e4uren, den sogenannten Codons. Jedes Triplett codiert f\u00fcr eine Aminos\u00e4ure, mit Ausnahme von drei &#8220;Stop&#8221;-Codons, die signalisieren, dass eine Aminos\u00e4urekette vollst\u00e4ndig ist. Prof. Dr. Edward Lemke und sein Team konnten eines dieser Stop-Codons so umprogrammieren, dass es eine neue Aminos\u00e4ure codiert, die nicht zu den 20 Aminos\u00e4uren geh\u00f6rt, die in lebenden Organismen nat\u00fcrlich vorkommen.&nbsp;IMAGE: Aleks Krolik\/EMBL<\/em><\/figcaption><\/figure>\n\n\n\n<p><br \/>Das Konzept kann m\u00f6glicherweise als Plattform f\u00fcr das Design weiterer Organellen dienen und einen Weg aufzeigen, um semisynthetische Zellen und semisynthetische Organismen zu schaffen. \u201eUnser Werkzeug ist in der Lage, Translation in Zellen durchzuf\u00fchren, potenziell aber auch andere Zellprozesse wie die Transkription. Dies k\u00f6nnte es uns erm\u00f6glichen, neue Typen von Organellen zu erzeugen, die das funktionelle Repertoire komplexer lebender Systeme erweitern\u201c, erl\u00e4utert Christopher Reinkemeier.<br \/><br \/>Die Designer-Organellen verbinden also Biologie und Chemie, um eine komplett neue chemische Funktionalit\u00e4t zu erreichen. Anwendungen ergeben sich au\u00dfer der erw\u00e4hnten Fluoreszenz-Methode f\u00fcr die Bildgebung etwa auch bei der Herstellung von Antik\u00f6rpern f\u00fcr therapeutische Zwecke. Zun\u00e4chst wollen Lemke und sein Team jedoch die Designer-Organellen weiter verkleinern, um jeden Einfluss auf die Physiologie eines gesunden Organismus zu minimieren.<br \/><br \/>Edward Lemke ist Visiting Group Leader am European Molecular Biology Laboratory, Professor f\u00fcr synthetische Biophysik an der Johannes Gutenberg-Universit\u00e4t Mainz und Adjunct Director am Institut f\u00fcr Molekulare Biologie. Er koordiniert auch das neue DFG-Schwerpunktprogramm \u201eMolekulare Mechanismen funktioneller Phasenseparation&#8221;.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL scientists create membraneless organelle to build proteins in living cell<\/p>\n","protected":false},"author":58,"featured_media":15532,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[791,43,358,792,1748,678],"embl_taxonomy":[],"class_list":["post-15466","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-designer","tag-heidelberg","tag-lemke","tag-organelle","tag-press-release","tag-translation"],"acf":{"article_intro":"<p>EMBL scientists create membraneless organelle to build proteins in living cell<\/p>\n","related_links":[{"link_description":"Research of the Lemke group at EMBL","link_url":"https:\/\/www.embl.de\/research\/units\/scb\/lemke\/index.html"}],"article_sources":[{"source_description":"<p>Reinkemeier, C.D.*, Girona, G.E.*, Lemke, E.A. \u2018Designer membraneless organelles enable codon reassignment of selected mRNAs in eukaryotes\u2019. <em>Science<\/em>, published online 29 March 2019.<br \/>\nDOI: http:\/\/dx.doi.org\/10.1126\/science.aaw2644<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1126\/science.aaw2644"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":[{"translation_language":"German","translation_anchor":"#a1"}],"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - 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