{"id":8995,"date":"2016-11-24T13:01:04","date_gmt":"2016-11-24T12:01:04","guid":{"rendered":"https:\/\/news.embl.de\/?p=8995"},"modified":"2024-03-25T10:15:07","modified_gmt":"2024-03-25T09:15:07","slug":"1611-stelzer","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/alumni\/1611-stelzer\/","title":{"rendered":"Thinking in 3D"},"content":{"rendered":"\n<p>For Ernst Stelzer, coming back to EMBL\u2019s Heidelberg campus \u201cis like coming back to an old friend.\u201d He arrived in the \u20181980s\u2019 as a physicist, and the innovative technologies developed by his teams have paved the way for biologists to further understand life at the microscopic level, and in unprecedented detail \u2013 from how neurons communicate with one another, to monitoring the beating heart of a fish. In recognition of his contributions, Stelzer was awarded this year\u2019s Lennart Philipson award by the EMBL Alumni Association.<\/p>\n\n\n\n<p>\u201cThe University of Frankfurt, where I am now based, may have been my alma mater,\u201d Stelzer says, \u201cbut let\u2019s face it: I spent 28 years here at EMBL.\u201d Among the first group of PhD students, Stelzer began at EMBL\u2019s Heidelberg site in 1983 working on confocal fluorescence microscopy. The atmosphere at EMBL was quite different back then. For one thing, the lab did not possess a single fluorescence microscope. Even then, \u201cin those days, it was not yet thought of as a quantitative tool or measuring device,\u201d Stelzer says. \u201cMicroscopy was more thought of as a way to just visualise something.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Back to basics<\/h2>\n\n\n\n<p>By 1993, together with his postdoc Stefan Hell, Stelzer had developed 4Pi microscopy. During the same year he and his PhD student Steffen Lindek patented and built confocal theta microscopes, a project that later involved James Swoger. By 1998 the team started to build something called a tetrahedral microscope, a machine that improved resolution using four lenses. Every calculation and equation they did over the years, though, brought them closer and closer to a striking revelation. The team realised that they could build a machine that would let them see life as never before. They set out in search of spare parts around the lab \u2013 an unused lens, a laser tucked away in a closet, a motor abandoned by a former postdoc. From these, they constructed an early version of a remarkable machine, one of the first implementations of light-sheet based fluorescence microscopy.<\/p>\n\n\n\n<p>The difference between traditional microscopy techniques and the machine Stelzer built can be illustrated using the example of imaging a developing fruit fly embryo. Previous microscopes would shine light evenly on the fly egg. And because its yolk is opaque, light would scatter and make it very difficult to see inside \u2013 let alone visualise it in 3D. Additionally, the&nbsp;amount of light used in the system can expose the specimen to up to 1000 times more energy than we typically receive from the sun. \u201cYou would not want to go to the beach in that!\u201d Stelzer jokes.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>We don\u2019t just look in one direction. We look at eight different directions in order to get a whole view of the specimen.<\/p><\/blockquote>\n\n\n\n<p>The new microscope overcame both of these obstacles. First, rather than repeatedly illuminating the entire fly \u2013 and frying it to a crisp \u2013 their microscope shone light through the egg in very thin slices, or planes. \u201cImaging in 3D is different than 2D,\u201d Stelzer says. \u201cWe don\u2019t just look in one direction. We look at eight different directions in order to get a whole view of the specimen.\u201d Scientists can then put these slices together using a computer and digitally recreate the specimen in 3D. And since less light energy is being used to image the egg at a time, the fly can survive imaging for days at a time. Selective plane illumination microscopy, or SPIM, was born.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">To boldly go\u2026<\/h2>\n\n\n\n<p>The next challenge was to convince other biologists. \u201cPeople seemed hesitant to try something so new at the time,\u201d Stelzer remembers. But <a href=\"https:\/\/news.embl.de\/alumni\/1608-jochen-wittbrodt\/\">EMBL alumnus Jochen Wittbrodt<\/a>, who was working with medaka fish, stepped up to the challenge. They brought on other students, including Sebastian Enders, Jan Huisken and Philipp Keller. Together, they did something no scientist had done before: see the inside of a live, intact fruit fly embryo, and image it in 3D.<\/p>\n\n\n\n<p>The results were astounding. Through thousands of images put together like a detailed flipbook, the team could clearly see and trace the organs as they developed inside the fly embryo \u2013 the pinching off of thorax and abdomen, the banding of rounded segments, the growth of the eyes. The whole period of imaging lasted seventeen hours. And what\u2019s more, the fly survived intact and was able to complete embryogenesis. Without delay, Stelzer and Steffen&nbsp;Lindek wrote a patent for SPIM and the team got to work on a prototype.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>Life is not flat \u2013 cells don\u2019t grow between a glass slide and cover slip. Cells grow on cells!<\/p><\/blockquote>\n\n\n\n<p>By the early 2000s what began as a side project became a full-time focus. The team had constructed a monolithic microscope carved out of a single block of aluminium. Later versions were built in increments with increasingly advanced lenses \u2013 and they even turned to German car manufacturers for other parts. \u201cThe motors that we ordered from one company were not even in the catalogue yet!\u201d Stelzer remembers.<\/p>\n\n\n\n<p>Applications of light-sheet based fluorescence microscopy have come a long way since this adventurous group of scientists were hacking&nbsp;parts together to think in 3D. Researchers can now use it to probe into deep tissue, such as in plants and zebrafish, as well as better understand diseases that affect humans, such as type 1 diabetes and congenital disorders. \u201cYou take on a different attitude toward your specimen when thinking in 3D,\u201d Stelzer says. \u201cLife is not flat \u2013 cells don\u2019t grow between a glass slide and cover slip. Cells grow on cells! The seeds of light-sheet based fluorescence microscopy were sown at EMBL \u2013 and thanks to the efforts of biologists, physicists, engineers and many other professionals, its applications are now being developed and used around the world.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Ernst Stelzer earns 2016 Lennart Philipson award for advances in light sheet microscopy<\/p>\n","protected":false},"author":39,"featured_media":8763,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5,17593],"tags":[80,91,55,43,79,27],"embl_taxonomy":[],"class_list":["post-8995","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-alumni","category-people-perspectives","tag-alumni","tag-biotechnology","tag-development","tag-heidelberg","tag-microscopy","tag-training"],"acf":{"article_intro":"<p>Ernst Stelzer earns 2016 <a href=\"https:\/\/www.embl.de\/aboutus\/alumni\/alumni-awards\/01_lpa\/index.html\">Lennart Philipson award<\/a> for advances in light sheet microscopy<\/p>\n","related_links":[{"link_description":"Lennart Philipson Award","link_url":"https:\/\/www.embl.de\/aboutus\/alumni\/alumni-awards\/01_lpa\/index.html"},{"link_description":"EMBL Alumni Relations","link_url":"https:\/\/www.embl.de\/aboutus\/alumni\/index.html"},{"link_description":"Stelzer group, Johann Wolfgang Goethe-Universit\u00e4t Frankfurt am Main","link_url":"http:\/\/www.physikalischebiologie.de\/"}],"article_sources":false,"vf_locked":false,"featured":false,"color":"#007B53"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Thinking in 3D | EMBL<\/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.embl.org\/news\/alumni\/1611-stelzer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Thinking in 3D | EMBL\" \/>\n<meta property=\"og:description\" content=\"Ernst Stelzer earns 2016 Lennart Philipson award for advances in light sheet microscopy\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/alumni\/1611-stelzer\/\" \/>\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=\"2016-11-24T12:01:04+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T09:15:07+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/11\/zebrafish.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"640\" \/>\n\t<meta property=\"og:image:height\" content=\"439\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Margaux Phares\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@mxphares\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Margaux Phares\" \/>\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\/alumni\/1611-stelzer\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/alumni\/1611-stelzer\/\"},\"author\":{\"name\":\"Margaux Phares\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/d1fced3e1bf469536cf90385bd640f83\"},\"headline\":\"Thinking in 3D\",\"datePublished\":\"2016-11-24T12:01:04+00:00\",\"dateModified\":\"2024-03-25T09:15:07+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/alumni\/1611-stelzer\/\"},\"wordCount\":953,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/alumni\/1611-stelzer\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/11\/zebrafish.jpg\",\"keywords\":[\"alumni\",\"biotechnology\",\"development\",\"heidelberg\",\"microscopy\",\"training\"],\"articleSection\":[\"Alumni\",\"People &amp; 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