{"id":29820,"date":"2020-07-08T11:59:00","date_gmt":"2020-07-08T09:59:00","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=29820"},"modified":"2025-07-14T14:17:36","modified_gmt":"2025-07-14T12:17:36","slug":"alpx","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/lab-matters\/alpx\/","title":{"rendered":"ALPX \u2013 smart crystallography"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\"><strong><em>EMBL spinoff ALPX provides technology to accelerate drug development<\/em><\/strong><\/h2>\n\n\n\n<p>Macromolecular crystallography has undergone an era of automation in the past two decades, which has revolutionised both crystallisation procedures and the use of beamlines. However, the important step of crystal harvesting has resisted that trend and remained a relatively slow manual process that could impact crystal quality. To address these shortcomings, scientists at EMBL Grenoble developed the CrystalDirect\u00ae technology as well as the web-based Crystallographic Information Management System (CRIMS) software. In combination they form the technological core of <a href=\"https:\/\/alpx-services.com\/\">ALPX<\/a> and enable a fully automated, remote-controlled protein-to-structure pipeline that can be piloted remotely from any computer anywhere.<\/p>\n\n\n\n<p>X-ray crystallography is still widely used to support drug design programmes in the pharma and biotech sectors. To do this, large numbers of crystals have to be produced, drug-like compounds added to them, followed by analysis using X-rays. While many steps in the process have been automated, crystal harvesting remains a manual and hence time-intense process. In addition, the manual process involves shipping samples from labs to synchrotron facilities and the transfer of large amounts of data.<\/p>\n\n\n\n<p>The ALPX concept combines automated crystal mounting with the CRIMS software to interconnect each of the steps in an automated way.&nbsp;\u201cWe can now access crystal structures faster than ever before \u2013 each cycle is done in days rather than weeks or months. This is opening up new possibilities for both structural biologists and medicinal chemists,\u201d&nbsp;says Irina Cornaciu, ALPX CEO, co-founder of ALPX and a scientist at <a href=\"https:\/\/embl.fr\/services\/ht_crystallisation\/index.html\">EMBL Grenoble<\/a>, who helped to develop the new technology. \u201cVirtually, we are making a highly automated crystallisation facility and a synchrotron facility available to scientists from their desktop computers.\u201d<\/p>\n\n\n\n<p>\u201cStructure-based drug design, which describes the development of new medications based on knowledge of the structure of the biological target, is essential in modern drug development. This targeted approach greatly reduces the cost and time for drug research, so new medications can be developed with less money and reach the market, and, ultimately the patient, earlier,\u201d says G\u00e1bor Lamm, Managing Director of <a href=\"https:\/\/embl-em.de\/\">EMBLEM<\/a>.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">The era of smart crystallography<\/h2>\n\n\n\n<p>In 2008, two researchers from EMBL Grenoble \u2013 Florent Cipriani and Jose Marquez \u2013 began growing crystals directly on a support compatible with subsequent data collection. This led to the establishment of the CrystalDirect\u00ae concept, which uses a robotic system developed at EMBL Grenoble to perform the necessary tasks.<\/p>\n\n\n\n<p>In the CrystalDirect\u00ae pipeline, crystals are grown on specialised plates \u2013 also developed at EMBL Grenoble \u2013 which are covered with a thin film on the bottom. The CRIMS software monitors the complete workflow and automatically analyses the data. The software allows researchers to take a look at the crystals on a computer screen and choose the best ones for further processing with CrystalDirect\u00ae. It also communicates with multiple synchrotrons in Europe to support automated and remote data collection.<\/p>\n\n\n\n<p>\u201cNot only is our approach much faster and more precise than harvesting by hand, it also prevents damage to the crystals, which often happens during manual handling. Our approach therefore ensures a higher crystal quality,\u201d explains Jose Marquez, the <a href=\"https:\/\/embl.fr\/services\/ht_crystallisation\/index.html\">head of the crystallisation facility at EMBL Grenoble<\/a> and co-founder of ALPX.<\/p>\n\n\n\n<p>Using the CRIMS software all steps can be controlled by scientists from their personal computer from anywhere in the world. This means that crystal measurements can be carried out without delays resulting from physical access to synchrotrons or the shipping of samples.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">ALPX is born<\/h2>\n\n\n\n<p>The CrystalDirect\u00aetechnology has been widely adopted and validated for research across EMBL\u2019s sites and further developed and refined over many years. During the entire development process, EMBLEM has been working side by side with the scientists behind CrystalDirect\u00ae and CRIMS. \u201cEMBLEM not only took care of securing intellectual property rights, such as patents, trademarks, and copyrights associated with the technology, but also helped to establish CrystalDirect\u00ae services for industrial partners,\u201d says J\u00fcrgen Bauer, Deputy Managing Director of <a href=\"https:\/\/embl-em.de\/\">EMBLEM<\/a>.<\/p>\n\n\n\n<p>\u201cOver the course of a few years, the attention and requests for services from third parties has increased to a level where spinning out the commercial CrystalDirect\u00ae services into a separate company became the logical next step,\u201d says Irina Cornaciu. \u201cALPX enables rapid and timely access to crystal structures for our partners, opening up new possibilities for medicinal chemistry.\u201d<\/p>\n\n\n\n<p>The <a href=\"https:\/\/www.embl.org\/news\/lab-matters\/empowering-european-structural-biology\/\">European Commission funded iNEXT programme<\/a> has been instrumental in prototyping the services and in promoting interactions with industry, which eventually led to the creation of ALPX.<\/p>\n\n\n<hr class=\"vf-divider\"\/>\n\n\n<h2 class=\"wp-block-heading\" id=\"french\">ALPX, spin-off de l&#8217;EMBL, propose une technologie permettant d\u2019acc\u00e9l\u00e9rer le d\u00e9veloppement de m\u00e9dicaments<\/h2>\n\n\n\n<p><strong><\/strong><strong>ALPX est la derni\u00e8re soci\u00e9t\u00e9 cr\u00e9\u00e9e par essaimage par le Laboratoire europ\u00e9en de biologie mol\u00e9culaire (EMBL) \u00e0 Grenoble. Elle propose des pipelines enti\u00e8rement automatis\u00e9s et t\u00e9l\u00e9command\u00e9s couvrant l\u2019ensemble du flux de travail de la prot\u00e9ine \u00e0 la structure, pour la cristallographie de prot\u00e9ines et le criblage de fragments et de compos\u00e9s. Leurs services \u00e0 haut d\u00e9bit permettent d&#8217;acc\u00e9der plus rapidement aux donn\u00e9es structurales, acc\u00e9l\u00e9rant ainsi la recherche dans de nombreux domaines de la pharmaceutique \u00e0 la biotechnologie. L\u2019entreprise a \u00e9t\u00e9 lanc\u00e9e avec l&#8217;aide de la branche de transfert de technologie de l&#8217;EMBL, EMBL Enterprise Management Technology Transfer GmbH (EMBLEM).<\/strong><\/p>\n\n\n\n<p>La cristallographie mol\u00e9culaire a connu une \u00e8re d&#8217;automatisation au cours des deux derni\u00e8res d\u00e9cennies, r\u00e9volutionnant \u00e0 la fois les laboratoires de cristallisation et les lignes de lumi\u00e8re. Cependant, l&#8217;\u00e9tape importante de la r\u00e9colte des cristaux a r\u00e9sist\u00e9 \u00e0 cette tendance et est rest\u00e9e un processus manuel relativement lent pouvant impacter la qualit\u00e9 des cristaux. Pour r\u00e9pondre \u00e0 ces besoins, des scientifiques de l\u2019EMBL Grenoble ont d\u00e9velopp\u00e9 la technologie CrystalDirect\u00ae et le logiciel en ligne Crystallographic Information Management System (CRIMS). &nbsp;Combin\u00e9s, ils constituent le c\u0153ur technologique d&#8217;ALPX et donnent acc\u00e8s \u00e0 un pipeline enti\u00e8rement automatis\u00e9 et contr\u00f4l\u00e9 \u00e0 distance, couvrant l\u2019ensemble du flux de travail de la prot\u00e9ine \u00e0 la structure.<\/p>\n\n\n\n<p>La cristallographie par rayons X est encore largement utilis\u00e9e pour soutenir les programmes de conception de m\u00e9dicaments dans les secteurs pharmaceutique et biotechnologique. Pour ce faire un grand nombre de cristaux doivent \u00eatre produits, auxquels des compos\u00e9s \u2013 potentiels m\u00e9dicaments &#8211; sont ajout\u00e9s, puis l\u2019ensemble est analys\u00e9 aux rayons X. Bien que de nombreuses \u00e9tapes du processus aient \u00e9t\u00e9 automatis\u00e9es, la r\u00e9colte des cristaux reste un processus manuel et donc long. En outre, le processus implique l&#8217;exp\u00e9dition d&#8217;\u00e9chantillons depuis chaque laboratoire vers les installations synchrotron et la r\u00e9cup\u00e9ration de grandes quantit\u00e9s de donn\u00e9es.<\/p>\n\n\n\n<p>Le concept d&#8217;ALPX combine le montage automatis\u00e9 des cristaux avec le logiciel CRIMS pour interconnecter chacune des \u00e9tapes. &#8220;Nous pouvons maintenant acc\u00e9der aux structures cristallines avec une rapidit\u00e9 sans pr\u00e9c\u00e9dent &#8211; chaque cycle se fait en quelques jours plut\u00f4t qu&#8217;en plusieurs semaines ou mois. Cela ouvre de nouvelles possibilit\u00e9s aux biologistes structurels et aux chimistes m\u00e9dicaux&#8221;, d\u00e9clare le Dr Irina Cornaciu, PDG d&#8217;ALPX et scientifique \u00e0 l&#8217;EMBL Grenoble, qui a contribu\u00e9 \u00e0 la mise au point de cette nouvelle technologie. &#8220;Nous mettons \u00e0 la disposition des scientifiques un service de cristallisation hautement automatis\u00e9 et un synchrotron, auxquels ils peuvent acc\u00e9der \u00e0 distance depuis leurs ordinateurs&#8221;.<\/p>\n\n\n\n<p>&#8220;Le d\u00e9veloppement de nouveaux m\u00e9dicaments gr\u00e2ce \u00e0 la connaissance de la structure de la cible biologique est une strat\u00e9gie essentielle au d\u00e9veloppement moderne de m\u00e9dicaments. Cette approche cibl\u00e9e permet de r\u00e9duire consid\u00e9rablement le co\u00fbt et le temps consacr\u00e9s \u00e0 la recherche sur les m\u00e9dicaments, de sorte que les nouveaux m\u00e9dicaments peuvent \u00eatre d\u00e9velopp\u00e9s avec moins d&#8217;argent et atteindre le march\u00e9, et donc le patient, plus t\u00f4t&#8221;, d\u00e9clare G\u00e1bor Lamm, directeur g\u00e9n\u00e9ral d\u2018EMBLEM.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">L&#8217;\u00e8re de la cristallographie intelligente<\/h2>\n\n\n\n<p>En 2008, deux chercheurs de l&#8217;EMBL Grenoble &#8211; Florent Cipriani et Jos\u00e9 M\u00e1rquez &#8211; ont commenc\u00e9 \u00e0 cultiver des cristaux directement sur un support compatible avec les \u00e9tapes ult\u00e9rieures de collecte de donn\u00e9es. Cette m\u00e9thode est \u00e0 l\u2019origine du concept CrystalDirect\u00ae, qui utilise un syst\u00e8me robotique d\u00e9velopp\u00e9 \u00e0 l&#8217;EMBL Grenoble pour effectuer les t\u00e2ches n\u00e9cessaires.<\/p>\n\n\n\n<p>Dans le pipeline CrystalDirect\u00ae, les cristaux sont cultiv\u00e9s sur des plaques recouvertes d\u2019une fine pellicule sp\u00e9cialement d\u00e9velopp\u00e9es \u00e0 l&#8217;EMBL Grenoble. Le logiciel CRIMS surveille l&#8217;ensemble du processus et analyse automatiquement les donn\u00e9es. Le logiciel permet aux chercheurs d&#8217;examiner les cristaux sur un \u00e9cran d&#8217;ordinateur, de s\u00e9lectionner les meilleurs pour une analyse ult\u00e9rieure avec CrystalDirect\u00ae. Il communique \u00e9galement avec plusieurs synchrotrons en Europe pour permettre une collecte des donn\u00e9es automatis\u00e9e et \u00e0 distance.<\/p>\n\n\n\n<p>&#8220;Non seulement notre approche est beaucoup plus rapide et pr\u00e9cise que la r\u00e9colte \u00e0 la main, mais elle permet \u00e9galement d&#8217;\u00e9viter d&#8217;endommager les cristaux, ce qui arrive souvent lors de la manipulation manuelle. Notre approche garantit donc une meilleure qualit\u00e9 des cristaux&#8221;, explique le Dr Jos\u00e9 M\u00e1rquez, responsable de l&#8217;installation de cristallisation de l&#8217;EMBL de Grenoble et co-fondateur d&#8217;ALPX.<\/p>\n\n\n\n<p>En utilisant le logiciel du CRIMS, toutes les \u00e9tapes peuvent \u00eatre contr\u00f4l\u00e9es par les scientifiques depuis leur ordinateur personnel, o\u00f9 qu&#8217;ils soient dans le monde. Ainsi, les mesures des cristaux peuvent \u00eatre effectu\u00e9es sans les delais r\u00e9sultant de l&#8217;acc\u00e8s physique aux synchrotrons ou de l&#8217;exp\u00e9dition des \u00e9chantillons.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">ALPX est n\u00e9e<\/h2>\n\n\n\n<p>La technologie CrystalDirect\u00ae a \u00e9t\u00e9 largement adopt\u00e9e et valid\u00e9e pour la recherche sur les sites de l&#8217;EMBL, puis d\u00e9velopp\u00e9e et perfectionn\u00e9e au fil des ans. Tout au long du processus de d\u00e9veloppement, EMBLEM a travaill\u00e9 au c\u00f4t\u00e9 des scientifiques \u00e0 l&#8217;origine de CrystalDirect\u00ae et du CRIMS.<\/p>\n\n\n\n<p>&#8220;EMBLEM s&#8217;est non seulement occup\u00e9e de la s\u00e9curisation des droits de propri\u00e9t\u00e9 intellectuelle, tels que les brevets, les marques d\u00e9pos\u00e9es et les droits d&#8217;auteur associ\u00e9s \u00e0 la technologie, mais a \u00e9galement contribu\u00e9 \u00e0 la mise en place des services CrystalDirect\u00ae pour les partenaires industriels&#8221;, d\u00e9clare J\u00fcrgen Bauer, directeur g\u00e9n\u00e9ral adjoint d&#8217;EMBLEM.<\/p>\n\n\n\n<p>&#8220;En quelques ann\u00e9es, l&#8217;attention et les demandes de services de la part de tiers ont augment\u00e9 \u00e0 tel point qu&#8217;il est devenu logique de transf\u00e9rer les services commerciaux CrystalDirect\u00ae dans une soci\u00e9t\u00e9 distincte&#8221;, explique Irina Cornaciu. &#8220;ALPX permet \u00e0 nos partenaires d&#8217;acc\u00e9der rapidement et en temps utile aux structures cristallines, ce qui ouvre de nouvelles possibilit\u00e9s pour la chimie m\u00e9dicinale&#8221;.<\/p>\n\n\n\n<p>Le programme iNEXT, financ\u00e9 par la Commission europ\u00e9enne, a contribu\u00e9 au prototypage des services et \u00e0 promouvoir les interactions avec l&#8217;industrie, ce qui a finalement conduit \u00e0 la cr\u00e9ation d&#8217;ALPX.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>The CrystalDirect\u00ae technology, combined with the web-based CRIMS software enable a fully automated, remote-controlled protein-to-structure pipeline.<\/p>\n","protected":false},"author":71,"featured_media":29856,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[3],"tags":[360,13985,29,303,37,967,33,361,754,4700,238],"embl_taxonomy":[9792],"class_list":["post-29820","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-lab-matters","tag-cipriani","tag-crystaldirect","tag-crystallography","tag-emblem","tag-grenoble","tag-inext","tag-instrumentation","tag-marquez","tag-robot","tag-spinoff","tag-technology-transfer","embl_taxonomy-embl-grenoble"],"acf":{"featured":true,"color":"#007B53","show_featured_image":false,"article_intro":"<p>ALPX has become the latest spinoff company from EMBL Grenoble. It offers fully automated and remote-controlled protein-to-structure pipelines for protein crystallography and fragment and compound screening. The ALPX high-throughput services enable researchers to solve crystal structures faster, thus accelerating research in a range of fields from pharma to biotech. The spinoff was launched with the assistance of EMBL\u2019s technology transfer arm, EMBLEM.<\/p>\n","article_sources":false,"related_links":[{"link_description":"","link_url":""},{"link_description":"","link_url":""},{"link_description":"","link_url":""},{"link_description":"","link_url":""},{"link_description":"","link_url":""}],"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","link_color":"#fff","press_contact":"EMBL Generic","vf_locked":false,"field_target_display":"","source_article":false,"field_article_language":{"value":"english","label":"English"},"article_translations":[{"translation_language":"Fran\u00e7ais","translation_anchor":""}],"languages":"","vfwp-news_embl_taxonomy":[9792]},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"8f81131e-d37c-470c-848f-618fce652295\";}","parents":[],"name":["EMBL Grenoble"],"slug":"embl-grenoble","description":"Where &gt; 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