{"id":71782,"date":"2019-05-21T12:42:09","date_gmt":"2019-05-21T17:42:09","guid":{"rendered":"https:\/\/uwm.edu\/news\/?p=71782"},"modified":"2019-06-03T13:53:11","modified_gmt":"2019-06-03T18:53:11","slug":"new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development","status":"publish","type":"post","link":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/","title":{"rendered":"New method simplifies search for protein receptor complexes, speeding drug development"},"content":{"rendered":"

MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell membranes. Receptors can change their molecular structure in a multitude of ways during binding \u2013 and only the right structure will \u201cunlock\u201d the drug\u2019s therapeutic effect.<\/p>\n

Now, a new method of assessing the actions of medicines by matching them to their unique protein receptors has the potential to greatly accelerate drug development and diminish the number of drug trials that fail during clinical trials.<\/p>\n

The method, developed by research teams from the University of Wisconsin-Milwaukee and the University of Glasgow, reduces the time and labor of finding the protein receptors \u201cwith the right response\u201d to drug candidates by several orders of magnitude.<\/p>\n

\u201cIt opens up a huge playing field for finding drug targets and drug stratification,\u201d\u00a0said Valerica Raicu, UW-Milwaukee professor of physics. \u201cUsing this method, we can characterize how each receptor responds differently to various drug candidates.\u201d<\/p>\n

The study appeared May 20 in the journal Nature Methods.<\/p>\n

The researchers\u2019 method tracks a chemical process called oligomerization that occurs when a receptor exists as a single subunit, but then shifts to a multi-structure \u2013 an oligomer \u2013 in the presence of the ligand (drug compound), or vice versa.<\/p>\n

\u201cWe used to think of these receptors as binary,\u201d said Raicu, who is lead author on the paper. \u201cThey were either activated by the compound or not. But now we are beginning to understand that, depending on the ligand, the same receptor can produce many different responses.\u201d<\/p>\n

The researchers first tested the method using fused florescent proteins produced by UW-Milwaukee assistant professor Ionel Popa. Then they validated the method on a receptor for a growth factor where malfunction is often linked to cancer\u00a0\u2013\u00a0the epidermal growth factor receptor (EGF). Activation of the receptor resulted in the generation of larger oligomers, as anticipated.<\/p>\n

The team then applied their method to a member of the G protein-coupled receptor (GPCR) family, a group of proteins that are targeted by a wide range of medicines.<\/p>\n

The effect of the association between ligands and receptors was shown in a matter of hours, compared to months using current technologies.<\/p>\n

\u201cThis new method of characterizing protein interactions will be important in the stratification of different medicines that target the same receptor,\u201d said Graeme Milligan, Gardiner Chair of Biochemistry at the University of Glasgow. \u201cIt will allow us to understand why some drug candidates are effective while others are not and can potentially be applied to different classes of proteins that are targets in the treatment of many diseases.\u201d<\/p>\n

The Raicu lab uses fluorescence-based imaging in order to see protein receptors in oligomeric states under various environmental conditions. Using single- or two-photon excitation microscopy, the researchers can produce a kind of road map of the various kinds of protein receptor oligomers in the absence or presence of ligands (or drugs) that bind to them.<\/p>\n

Researchers image protein-receptor molecules by attaching florescent tags. This way, single-molecule protein receptors give off light when they pass under a laser and are excited, and those bursts are recorded with a camera. Receptor oligomers give off a more intense burst of light, and those are also photographed.<\/p>\n

\u201cNow you can graph the intensity and the number of bursts,\u201d said Raicu, \u201cand see how many are associated into oligomers \u2013 how big they are \u2013 and where they are in the sample. After adding the ligand, you can see whether it promotes association of single molecules of receptor proteins into oligomers, or the breakdown\u00a0of oligomers\u00a0into the former.<\/p>\n

See the paper at: https:\/\/www.nature.com\/articles\/s41592-019-0408-9<\/a><\/p>\n

For more information, contact\u00a0Valerica Raicu at vraicu@uwm.edu<\/a>,\u00a0414-229-4969.<\/p>\n","protected":false},"excerpt":{"rendered":"

MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell membranes. Receptors can change their molecular structure in a multitude of ways during binding \u2013 and only the right structure will \u201cunlock\u201d the drug\u2019s therapeutic effect. Now, a new […]<\/p>\n","protected":false},"author":836,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","uwm_wg_additional_authors":[]},"categories":[202],"tags":[],"section":[],"display_categories":[],"related-coverage":[],"uwmnews-feed":[],"class_list":["post-71782","post","type-post","status-publish","format-standard","hentry","category-news-releases"],"uwm_unpublish_requested":false,"yoast_head":"\nNew method simplifies search for protein receptor complexes, speeding drug development<\/title>\n<meta name=\"description\" content=\"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"New method simplifies search for protein receptor complexes, speeding drug development\" \/>\n<meta property=\"og:description\" content=\"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell\" \/>\n<meta property=\"og:url\" content=\"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/\" \/>\n<meta property=\"og:site_name\" content=\"UWM REPORT\" \/>\n<meta property=\"article:published_time\" content=\"2019-05-21T17:42:09+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2019-06-03T18:53:11+00:00\" \/>\n<meta name=\"author\" content=\"Laura L Otto\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@UWMNews\" \/>\n<meta name=\"twitter:site\" content=\"@UWMNews\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Laura L Otto\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/\"},\"author\":{\"name\":\"Laura L Otto\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#\\\/schema\\\/person\\\/2f360a26f3df4ff8f31b58e43d772565\"},\"headline\":\"New method simplifies search for protein receptor complexes, speeding drug development\",\"datePublished\":\"2019-05-21T17:42:09+00:00\",\"dateModified\":\"2019-06-03T18:53:11+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/\"},\"wordCount\":631,\"publisher\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#organization\"},\"articleSection\":[\"News Releases\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/\",\"url\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/\",\"name\":\"New method simplifies search for protein receptor complexes, speeding drug development\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#website\"},\"datePublished\":\"2019-05-21T17:42:09+00:00\",\"dateModified\":\"2019-06-03T18:53:11+00:00\",\"description\":\"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell\",\"breadcrumb\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\\\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/uwm.edu\\\/news\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"New method simplifies search for protein receptor complexes, speeding drug development\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#website\",\"url\":\"https:\\\/\\\/uwm.edu\\\/news\\\/\",\"name\":\"UWM REPORT\",\"description\":\"News from the University of Wisconsin - Milwaukee\",\"publisher\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#organization\"},\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/uwm.edu\\\/news\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Organization\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#organization\",\"name\":\"University of Wisconsin-Milwaukee\",\"url\":\"https:\\\/\\\/uwm.edu\\\/news\\\/\",\"logo\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#\\\/schema\\\/logo\\\/image\\\/\",\"url\":\"https:\\\/\\\/uwm.edu\\\/news\\\/wp-content\\\/uploads\\\/sites\\\/41\\\/2017\\\/02\\\/uwm-seo-logo.jpg\",\"contentUrl\":\"https:\\\/\\\/uwm.edu\\\/news\\\/wp-content\\\/uploads\\\/sites\\\/41\\\/2017\\\/02\\\/uwm-seo-logo.jpg\",\"width\":225,\"height\":224,\"caption\":\"University of Wisconsin-Milwaukee\"},\"image\":{\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#\\\/schema\\\/logo\\\/image\\\/\"},\"sameAs\":[\"https:\\\/\\\/x.com\\\/UWMNews\"]},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/uwm.edu\\\/news\\\/#\\\/schema\\\/person\\\/2f360a26f3df4ff8f31b58e43d772565\",\"name\":\"Laura L Otto\",\"url\":\"https:\\\/\\\/uwm.edu\\\/news\\\/author\\\/llhuntuwm-edu\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"New method simplifies search for protein receptor complexes, speeding drug development","description":"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/","og_locale":"en_US","og_type":"article","og_title":"New method simplifies search for protein receptor complexes, speeding drug development","og_description":"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell","og_url":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/","og_site_name":"UWM REPORT","article_published_time":"2019-05-21T17:42:09+00:00","article_modified_time":"2019-06-03T18:53:11+00:00","author":"Laura L Otto","twitter_card":"summary_large_image","twitter_creator":"@UWMNews","twitter_site":"@UWMNews","twitter_misc":{"Written by":"Laura L Otto","Est. reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/#article","isPartOf":{"@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/"},"author":{"name":"Laura L Otto","@id":"https:\/\/uwm.edu\/news\/#\/schema\/person\/2f360a26f3df4ff8f31b58e43d772565"},"headline":"New method simplifies search for protein receptor complexes, speeding drug development","datePublished":"2019-05-21T17:42:09+00:00","dateModified":"2019-06-03T18:53:11+00:00","mainEntityOfPage":{"@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/"},"wordCount":631,"publisher":{"@id":"https:\/\/uwm.edu\/news\/#organization"},"articleSection":["News Releases"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/","url":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/","name":"New method simplifies search for protein receptor complexes, speeding drug development","isPartOf":{"@id":"https:\/\/uwm.edu\/news\/#website"},"datePublished":"2019-05-21T17:42:09+00:00","dateModified":"2019-06-03T18:53:11+00:00","description":"MILWAUKEE_For a drug to intervene in cells or entire organs that are not behaving normally, it must first bind to specific protein receptors in the cell","breadcrumb":{"@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/uwm.edu\/news\/new-method-simplifies-the-search-for-protein-receptor-complexes-speeding-drug-development\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/uwm.edu\/news\/"},{"@type":"ListItem","position":2,"name":"New method simplifies search for protein receptor complexes, speeding drug development"}]},{"@type":"WebSite","@id":"https:\/\/uwm.edu\/news\/#website","url":"https:\/\/uwm.edu\/news\/","name":"UWM REPORT","description":"News from the University of Wisconsin - Milwaukee","publisher":{"@id":"https:\/\/uwm.edu\/news\/#organization"},"potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/uwm.edu\/news\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Organization","@id":"https:\/\/uwm.edu\/news\/#organization","name":"University of Wisconsin-Milwaukee","url":"https:\/\/uwm.edu\/news\/","logo":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/uwm.edu\/news\/#\/schema\/logo\/image\/","url":"https:\/\/uwm.edu\/news\/wp-content\/uploads\/sites\/41\/2017\/02\/uwm-seo-logo.jpg","contentUrl":"https:\/\/uwm.edu\/news\/wp-content\/uploads\/sites\/41\/2017\/02\/uwm-seo-logo.jpg","width":225,"height":224,"caption":"University of Wisconsin-Milwaukee"},"image":{"@id":"https:\/\/uwm.edu\/news\/#\/schema\/logo\/image\/"},"sameAs":["https:\/\/x.com\/UWMNews"]},{"@type":"Person","@id":"https:\/\/uwm.edu\/news\/#\/schema\/person\/2f360a26f3df4ff8f31b58e43d772565","name":"Laura L Otto","url":"https:\/\/uwm.edu\/news\/author\/llhuntuwm-edu\/"}]}},"acf":[],"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/posts\/71782","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/users\/836"}],"replies":[{"embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/comments?post=71782"}],"version-history":[{"count":2,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/posts\/71782\/revisions"}],"predecessor-version":[{"id":72084,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/posts\/71782\/revisions\/72084"}],"wp:attachment":[{"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/media?parent=71782"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/categories?post=71782"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/tags?post=71782"},{"taxonomy":"section","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/section?post=71782"},{"taxonomy":"display_categories","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/display_categories?post=71782"},{"taxonomy":"related-coverage","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/related-coverage?post=71782"},{"taxonomy":"uwmnews-feed","embeddable":true,"href":"https:\/\/uwm.edu\/news\/wp-json\/wp\/v2\/uwmnews-feed?post=71782"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}