{"id":2860,"date":"2014-12-09T10:15:47","date_gmt":"2014-12-09T09:15:47","guid":{"rendered":"http:\/\/news.embl.de\/?p=2860"},"modified":"2024-11-29T16:55:55","modified_gmt":"2024-11-29T15:55:55","slug":"1412_snaptag","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/","title":{"rendered":"Delighting in detail"},"content":{"rendered":"\n

\u201cAlready we\u2019ve been able to see things that we couldn\u2019t see before. Structures such as nerves arranged around a hair on the skin; we can now see<\/em> them under the microscope, just as they were presumed to be,\u201d says Paul Heppenstall of a new technique developed by his lab.<\/p>\n\n\n\n

Already we\u2019ve been able to see things that we couldn\u2019t see before<\/p><\/blockquote>\n\n\n\n

The technique, called SNAP-tagging, relies on a small protein that binds to a specific small chemical structure \u2013 and once bound, it won\u2019t let go. Guoying Yang and Fernanda de Castro Reis in the Heppenstall lab genetically engineered mice so that their cells would produce that SNAP protein. They then used fluorescent probes that contain the small chemical that SNAP binds to, and injected them into the mice. SNAP acts like an anchor, glueing the probes in place for researchers to follow under the microscope. The approach had been used for about a decade in studies using cell cultures \u2013 cells grown a lab dish \u2013 but Heppenstall\u2019s group is the first to apply it to neurons in living mice. Very often, expanding a technique from lab dish to live animal presents a whole host of challenges, as a mouse is much more than just a group of cells. But with SNAP, the scientists found, mice actually eliminate a significant hurdle themselves.<\/p>\n\n\n\n

\"Nerves
Nerves arranged around a hair on the skin, “just as they were presumed to be.” IMAGE: EMBL\/L.CASTALDI<\/figcaption><\/figure><\/div>\n\n\n\n

\u201cIf we\u2019d gone straight for the mouse, there would have been fewer challenges!\u201d Heppenstall says with hindsight. \u201cBut we tried to do everything step-by-step. So we started with cell culture, and found that the probes are very sticky \u2013 you have to wash the cells repeatedly to get rid of tags that are floating around, not attached to SNAP, before you can see anything. Then we took tissue from animals, and tried to label that, and they were still sticky. And then finally we got around to injecting into the mouse \u2013 and it just worked! It turns out that the mouse is very good at washing out what it doesn\u2019t need \u2013 so all the probes get washed out, except the ones bound to SNAP.\u201d<\/p>\n\n\n\n

finally we got around to injecting into the mouse \u2013 and it just worked!<\/p><\/blockquote>\n\n\n\n

The will to keep trying to find ways to make the strategy work was driven by the Heppenstall lab\u2019s particular interest: the nerves in the skin. Even though they are all over our bodies, and skin samples are relatively easy to maintain in a lab dish, these nerves are actually incredibly difficult to study under the microscope. The skin has properties that almost seem designed to thwart conventional microscopy approaches. Under blue light, it naturally glows green, so attempting to label any structures \u2013 like nerves \u2013 in the skin with fluorescent proteins has an obvious hitch: it\u2019s hard to distinguish between the glow from your labels and the skin\u2019s own. The alternative approach would be to use antibodies \u2013 molecules our immune system uses to identify invaders, and which can be co-opted to home in on and tag particular structures. But the skin\u2019s main function is to be a barrier, to protect us from the outside world. So it is very impermeable, which means it\u2019s very difficult to get large molecules like antibodies through.<\/p>\n\n\n\n

\"Previous
Previous approaches that relied on antibodies had difficulty penetrating the skin.
IMAGE: EMBL\/R. DHANDAPANI<\/figcaption><\/figure><\/div>\n\n\n\n

SNAP-tag overcomes these problems, as it allows researchers to use virtually any labels they want, including artificial dies of different colours that stand out from the skin\u2019s background glow, and are small enough to make it into the skin. And because these are artificial, custom-made probes, they can be designed to do more than just highlight particular structures. You can have probes that destroy certain structures or cells, for instance. As Heppenstall puts it, \u201cwith SNAP-tag you can do almost anything, as long as the chemistry to make the probe is possible.\u201d<\/p>\n\n\n\n

\"Researchers
Researchers can now use custom-made artificial labels, obtaining much more detailed images of the skin\u2019s nerves. IMAGE: EMBL\/F. C. REIS<\/figcaption><\/figure><\/div>\n\n\n\n

That joining of forces between experts in biology and in chemistry is essential to develop and expand approaches like SNAP. Chemical biologist Kai Johnsson and his lab at the \u00c9cole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), in Switzerland, were instrumental in this work. And Yang\u2019s postdoc position is shared between the Heppenstall lab and Carsten Schultz\u2019s group at EMBL Heidelberg, which focuses on chemical biology. The two EMBL groups are continuing to explore SNAP-tagging\u2019s potential, looking to develop tags to see the unseen.<\/p>\n\n\n\n

Ultimately, Heppenstall wants to record activity in individual neurons. He\u2019d like to move a hair on a patch of mouse skin, or change the skin\u2019s temperature, and watch that information flow through the nerve, to the next nerve, tracking it throughout the whole network. In principle, he speculates, you could do this in a whole brain, or a whole animal. It would be like a taking a scan and zooming in to see what\u2019s happening inside<\/em> each nerve cell.<\/p>\n\n\n\n

\"\u201cThis
\u201cThis is my favorite image \u2013 we’d never seen anything like this until we used this technique,\u201d says Heppenstall. \u201cIt shows that free nerve endings [red] in the skin split into an incredible number of branches.\u201d IMAGE: EMBL\/S. MORLEY<\/figcaption><\/figure><\/div>\n\n\n\n

Right now, Heppenstall and colleagues are simply delighting in their new-found detail. \u201cThe first thing we\u2019re doing is just exploring in more detail \u2013 going to higher resolution and just looking to see which nerves go where. In the future we hope to use this as a map when assigning functions to different neurons, to understand more about how our sense of touch works.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

Unprecedented detail in images of mouse neurons thanks to new SNAP-tagging microscopy technique.<\/p>\n","protected":false},"author":8,"featured_media":2861,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[49,69,79,74,67,57,1748,514],"embl_taxonomy":[],"class_list":["post-2860","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-interdisciplinary","tag-methods","tag-microscopy","tag-monterotondo","tag-neurobiology","tag-postdoc","tag-press-release","tag-rome"],"acf":{"article_intro":"

The skin seems almost designed to thwart established microscopy techniques, but a new approach by scientists at EMBL Monterotondo\u00a0overcomes such challenges, showing mouse neurons as never before.<\/p>\n","related_links":[{"link_description":"The EMBL Interdisciplinary Postdoc Programme","link_url":"https:\/\/www.embl.org\/about\/info\/postdoctoral-programme\/eipod4-fellowship-programme\/"},{"link_description":"The Johnsson lab at EPFL","link_url":"https:\/\/www.epfl.ch\/labs\/lip\/johnsson\/"}],"article_sources":[{"source_description":"

Yang, Reis\u00a0et al<\/em>.\u00a0Nature Methods,\u00a0<\/em>8 December 2014. DOI: 10.1038\/nmeth.3207.<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1038\/nmeth.3207"}],"show_featured_image":false,"vf_locked":false,"featured":false,"in_this_article":false,"color":"#007B53","youtube_url":"","mp4_url":"","video_caption":"","press_contact":"EMBL Generic","field_target_display":"embl","source_article":false},"embl_taxonomy_terms":[],"yoast_head":"\nDelighting in detail | EMBL<\/title>\n<meta name=\"description\" content=\"Unprecedented detail in images of mouse neurons thanks to new SNAP-tagging microscopy technique.\" \/>\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.embl.org\/news\/science\/1412_snaptag\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Delighting in detail | EMBL\" \/>\n<meta property=\"og:description\" content=\"Unprecedented detail in images of mouse neurons thanks to new SNAP-tagging microscopy technique.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2014-12-09T09:15:47+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-11-29T15:55:55+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/12\/1412_snaptag_1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Sonia Furtado Neves\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@Aur_ora\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Sonia Furtado Neves\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"5 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\"},\"author\":{\"name\":\"Sonia Furtado Neves\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/d926199a955624b44dda296f396c5e68\"},\"headline\":\"Delighting in detail\",\"datePublished\":\"2014-12-09T09:15:47+00:00\",\"dateModified\":\"2024-11-29T15:55:55+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\"},\"wordCount\":966,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/12\/1412_snaptag_1.jpg\",\"keywords\":[\"interdisciplinary\",\"methods\",\"microscopy\",\"monterotondo\",\"neurobiology\",\"postdoc\",\"press release\",\"rome\"],\"articleSection\":[\"Science\",\"Science & Technology\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\",\"url\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\",\"name\":\"Delighting in detail | EMBL\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/12\/1412_snaptag_1.jpg\",\"datePublished\":\"2014-12-09T09:15:47+00:00\",\"dateModified\":\"2024-11-29T15:55:55+00:00\",\"description\":\"Unprecedented detail in images of mouse neurons thanks to new SNAP-tagging microscopy technique.\",\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1412_snaptag\/#primaryimage\",\"url\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/12\/1412_snaptag_1.jpg\",\"contentUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2014\/12\/1412_snaptag_1.jpg\",\"width\":620,\"height\":425,\"caption\":\"A bundle of nerves that relays information from touch receptors on the skin to the spinal cord and ultimately the brain, imaged with the new technique. 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