{"id":5347,"date":"2022-03-10T16:15:32","date_gmt":"2022-03-10T15:15:32","guid":{"rendered":"http:\/\/v2tbi.christelle-labruyere.com\/?page_id=5347"},"modified":"2022-06-08T19:27:42","modified_gmt":"2022-06-08T17:27:42","slug":"ingenierie-moleculaire","status":"publish","type":"page","link":"https:\/\/www.toulouse-biotechnology-institute.fr\/en\/poles\/equipe-i2m\/ingenierie-moleculaire\/","title":{"rendered":"Ing\u00e9nierie Mol\u00e9culaire"},"content":{"rendered":"\t\t
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Equipe I2M<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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Th\u00e8me \"Ing\u00e9nierie Mol\u00e9culaire\" <\/h1>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t
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Quelques mots sur le th\u00e8me<\/h3>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Une expertise dans l'ing\u00e9nierie des prot\u00e9ines membranaires d\u2019oxydor\u00e9duction<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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L\u2019\u00e9quipe I2M est \u00e9galement reconnue pour son savoir-faire dans le domaine de l\u2019ing\u00e9nierie des prot\u00e9ines, en particulier les cytochromes P450 et leurs donneurs d\u2019\u00e9lectrons. Nous avons d\u00e9velopp\u00e9 des approches originales de cr\u00e9ation de banques combinatoires et de cartographie fonctionnelle des enzymes modifi\u00e9s. Les m\u00e9thodes d\u2019ing\u00e9nierie que nous utilisons visent soit des enzymes individuelles (modification des activit\u00e9s des enzymes naturelles, ing\u00e9nierie des sites actifs ou de reconnaissance) soit des assemblages macromol\u00e9culaires (formation de complexes r\u00e9dox, formation de la coque des microcompartiments bact\u00e9riens, assemblages d\u2019enzymes individuels). L\u2019ing\u00e9nierie mol\u00e9culaire est parfaitement int\u00e9gr\u00e9e au th\u00e8me ing\u00e9nierie m\u00e9tabolique car les deux poursuivent le m\u00eame objectif\u00a0: obtenir des syst\u00e8mes m\u00e9taboliques synth\u00e9tiques efficaces. Les mod\u00e8les enzymatiques utilis\u00e9s sont des oxydases (cytochromes P450), des terp\u00e8nes synth\u00e9tases et les enzymes de la voie de production des carot\u00e9no\u00efdes (d\u00e9saturases, cyclases, dioxyg\u00e9nases, etc.).<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t

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Les projets<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t
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Bacterial Microcompartments<\/strong><\/p>

La synth\u00e8se continue exige le d\u00e9veloppement de nouveaux outils biotechnologiques pour am\u00e9liorer l’efficacit\u00e9 des cascades m\u00e9taboliques cr\u00e9\u00e9es dans des micro-organismes donn\u00e9s. Deux strat\u00e9gies majeures pour atteindre cet objectif sont la colocalisation spatiale des enzymes con\u00e7ues et l’optimisation de leur orientation relative. Dans ce sens, notre premi\u00e8re intention est d’apprendre de la nature, en contribuant \u00e0 notre compr\u00e9hension de la fonction des micro-compartiments bact\u00e9riens (BMC). Les BMC sont des assemblages macromol\u00e9culaires qui encapsulent naturellement des enzymes qui participent \u00e0 divers processus m\u00e9taboliques. Nous \u00e9tudions par divers moyens biophysiques le m\u00e9canisme qui conduit \u00e0 l’assemblage de la coquille des BMC. L’objectif du second axe de ce projet est d’\u00e9tablir la composition pr\u00e9cise des unit\u00e9s d’assemblage naturelles pour ensuite concevoir de nouvelles plateformes hexam\u00e9riques.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Combinatoire des s\u00e9quences linkers sur l\u2019activit\u00e9 des prot\u00e9ines fusions artificielles<\/strong>.<\/p>

\u00a0<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Projet <\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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Dynamique entre domaines au sein d\u2019une oxidor\u00e9ductase multidomaine<\/strong><\/p>

Dans l’organisme, les m\u00e9dicaments subissent un m\u00e9tabolisme sp\u00e9cifique qui s’effectue principalement par les enzymes P450. Une seule flavoenzyme, la NADPH-cytochrome P450 r\u00e9ductase (CPR), donne les \u00e9lectrons n\u00e9cessaires aux P450s pour leur catalyse. Jusqu’\u00e0 pr\u00e9sent, la plupart des variations interindividuelles de ce m\u00e9tabolisme ont \u00e9t\u00e9 \u00e9tudi\u00e9es sur les polymorphismes du P450. Les modifications de l’\u00e9quilibre conformationnel de la CPR, caus\u00e9es soit par des mutations, soit par l’interaction avec de petites mol\u00e9cules, peuvent augmenter son affinit\u00e9 pour un P450 sp\u00e9cifique, au d\u00e9triment des autres. L’objectif de ce projet est de d\u00e9chiffrer les facteurs (membrane du reticulum endoplasmique, \u00e9tat d’oxydation et variantes polymorphes de la CPR) qui contr\u00f4lent les modifications structurales et la dynamique de la CPR ancr\u00e9e dans la membrane et leur implication dans le m\u00e9tabolisme des m\u00e9dicaments et les d\u00e9ficiences fonctionnelles potentielles. Ce projet vise \u00e0 fournir de nouveaux outils pour d\u00e9crypter les facteurs mol\u00e9culaires modulant le paysage dynamique de la CPR et la sp\u00e9cificit\u00e9 des interactions dans les complexes CPR\/P450.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Projet AlphaFold2<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t
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AlphaFold et complexes prot\u00e9iques<\/strong><\/p>

AlphaFold2, an AI deep-learning system developed by DeepMind surpasses in accuracy all previous computing attempts for protein structure predictions. Recent versions were successfully extended to\u00a0\u00a0 modeling of protein complexes including in some instances the potential to address large scale conformational changes involved in catalysis. DeepMind and EMBL\u2019s European Bioinformatics Institute (EMBL-EBI) have partnered to create AlphaFold Protein Structure DataBase (ADB) that covers the complete human and 47 other key organisms (mouse, yeast, Arabidopsis, etc.), as well as the manually curated UniProt database. As of April 2022, AlphaFold DB provides open access to 992,316 protein 3D structure entries, most of them with no experimental structure available. We are using AlphaFold2_advanced version to look at the structures of complexes between P450 enzymes and P450-associated redox proteins and to their alternative geometries.<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t

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Equipe I2M Retour vers l’\u00e9quipe Th\u00e8me “Ing\u00e9nierie Mol\u00e9culaire” Quelques mots sur le th\u00e8me Une expertise dans l’ing\u00e9nierie des prot\u00e9ines membranaires d\u2019oxydor\u00e9duction L\u2019\u00e9quipe I2M est \u00e9galement reconnue pour son savoir-faire dans le domaine de l\u2019ing\u00e9nierie des prot\u00e9ines, en particulier les cytochromes P450 et leurs donneurs d\u2019\u00e9lectrons. Nous avons d\u00e9velopp\u00e9 des approches originales de cr\u00e9ation de banques […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":5039,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-5347","page","type-page","status-publish","hentry"],"yoast_head":"\nIng\u00e9nierie Mol\u00e9culaire | TBI, Toulouse Biotechnology Institute<\/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.toulouse-biotechnology-institute.fr\/en\/poles\/equipe-i2m\/ingenierie-moleculaire\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Ing\u00e9nierie Mol\u00e9culaire | TBI, Toulouse Biotechnology Institute\" \/>\n<meta property=\"og:description\" content=\"Equipe I2M Retour vers l’\u00e9quipe Th\u00e8me “Ing\u00e9nierie Mol\u00e9culaire” Quelques mots sur le th\u00e8me Une expertise dans l’ing\u00e9nierie des prot\u00e9ines membranaires d\u2019oxydor\u00e9duction L\u2019\u00e9quipe I2M est \u00e9galement reconnue pour son savoir-faire dans le domaine de l\u2019ing\u00e9nierie des prot\u00e9ines, en particulier les cytochromes P450 et leurs donneurs d\u2019\u00e9lectrons. Nous avons d\u00e9velopp\u00e9 des approches originales de cr\u00e9ation de banques […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.toulouse-biotechnology-institute.fr\/en\/poles\/equipe-i2m\/ingenierie-moleculaire\/\" \/>\n<meta property=\"og:site_name\" content=\"TBI, Toulouse Biotechnology Institute\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/TBI-Toulouse-Biotechnology-Institute-Bio-Chemical-Engineering-360428497952306\" \/>\n<meta property=\"article:modified_time\" content=\"2022-06-08T17:27:42+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.toulouse-biotechnology-institute.fr\/wp-content\/uploads\/2022\/03\/Ingenierie-Proteines-I2M.png\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:site\" content=\"@TBI_Biotech\" \/>\n<meta name=\"twitter:label1\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/\",\"url\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/\",\"name\":\"Ing\u00e9nierie Mol\u00e9culaire | TBI, Toulouse Biotechnology Institute\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/#primaryimage\"},\"image\":{\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/wp-content\\\/uploads\\\/2022\\\/03\\\/Ingenierie-Proteines-I2M.png\",\"datePublished\":\"2022-03-10T15:15:32+00:00\",\"dateModified\":\"2022-06-08T17:27:42+00:00\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/#breadcrumb\"},\"inLanguage\":\"en-GB\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-GB\",\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/#primaryimage\",\"url\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/wp-content\\\/uploads\\\/2022\\\/03\\\/Ingenierie-Proteines-I2M.png\",\"contentUrl\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/wp-content\\\/uploads\\\/2022\\\/03\\\/Ingenierie-Proteines-I2M.png\"},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/ingenierie-moleculaire\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Accueil\",\"item\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Poles\",\"item\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Equipe I2M\",\"item\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/poles\\\/equipe-i2m\\\/\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Ing\u00e9nierie Mol\u00e9culaire\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/#website\",\"url\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/\",\"name\":\"TBI, Toulouse Biotechnology Institute\",\"description\":\"Bio & Chemical Engineering\",\"publisher\":{\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/#organization\"},\"alternateName\":\"TBI, Toulouse Biotechnology Institute\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-GB\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/www.toulouse-biotechnology-institute.fr\\\/#organization\",\"name\":\"TBI - 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