{"id":69913,"date":"2024-08-27T13:45:19","date_gmt":"2024-08-27T11:45:19","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=69913"},"modified":"2024-08-27T13:55:57","modified_gmt":"2024-08-27T11:55:57","slug":"seeing-into-the-depths","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/seeing-into-the-depths\/","title":{"rendered":"Seeing into the depths"},"content":{"rendered":"\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Summary    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li>Neuroscientists have sought to better understand brain function but lacked the capability to observe neuronal activity deep within the brain.<\/li>\r\n \t<li>EMBL scientists applied rational molecular engineering to develop photoacoustic probes that can be used deep within brain tissue to label and visualise neurons.<\/li>\r\n \t<li>This imaging approach expands significantly on what neuroscientists have been able to see with conventional light microscopy, offering the potential to report on deep neuron activity and better understand brain function.<\/li>\r\n \t<li>This research represents a first proof of principle for a dynamic observation tool that could significantly improve our understanding of brain function.<\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>To understand the brain better, we need new methods to observe its activity.<\/p>\n\n\n\n<p>That is at the heart of a molecular engineering project, spearheaded by two EMBL research groups, that has resulted in a novel approach to create photoacoustic probes for neuroscience applications. The findings were published in the<em> Journal of the American Chemical Society<\/em>.<\/p>\n\n\n\n<p>\u201cPhotoacoustics offer a way to capture imagery of an entire mouse brain, but we just lacked the right probes to visualise a neuron\u2019s activity,\u201d said Robert Prevedel, an EMBL group leader and a senior author on this paper. To overcome this technological challenge, he worked with Claire Deo, another EMBL group leader and also a senior author on the paper. She and her team specialise in chemical engineering.&nbsp;<\/p>\n\n\n\n<p>\u201cWe have been able to show that we can actually label neurons in specific brain areas with probes bright enough to be detected by our customised photoacoustic microscope,\u201d Prevedel said.<\/p>\n\n\n\n<p>Scientists can learn more about biological processes by tracking certain chemicals, such as ions or biomolecules. Photoacoustic probes can act as &#8216;reporters&#8217; for hard-to-detect chemicals by binding to them specifically. The probes can then absorb light when excited by lasers and emit sound waves that can be detected by specialised imaging equipment. For neuroscience applications, however, researchers have so far been unable to engineer targeted reporters that can visualise brain functions tailored for photoacoustics.<\/p>\n\n\n\n<p>While researchers have experimented with using synthetic dyes as photoacoustic reporters of neuronal activity, controlling where the dye goes and what might be labelled has been challenging. Proteins have been particularly useful as probes for tagging specific molecules, but have not yet led to effective photoacoustic probes to monitor neural activity across the entire brain.<\/p>\n\n\n\n<p>\u201cIn our case, we took the best of both of these sensors, combining a protein with a rationally designed synthetic dye, and we can now label and visualise neurons in specific regions of interest,\u201d said Alexander Cook, first author of the study and a predoctoral fellow in the Deo group. In rational design approaches, researchers use existing knowledge and principles to build molecules with the desired properties, instead of blindly making and testing random compounds. \u201cAlso, we\u2019re not just talking about a static observation, but instead this probe shows a reversible, dynamic response to calcium, which is a marker of neuron activity,\u201d Cook added.&nbsp;<\/p>\n\n\n\n<p>According to Deo, an important challenge stood in the way of this technological development. Because photoacoustic probes have not been extensively studied, the researchers lacked a way to evaluate the probes they were building.<\/p>\n\n\n\n<p>Consequently, the project began with Nikita Kaydanov, co-author of the study and predoctoral fellow in the Prevedel Group, who<a href=\"https:\/\/www.embl.org\/news\/picture-of-the-week\/spotlight-using-light-and-sound-to-see-into-the-brain\/\"> custom-made a spectroscopy setup<\/a>. \u201cThere is no commercial setup that can measure photoacoustic signals of a probe in test tubes or cuvettes, so we had to build one,\u201d Kaydanov said. \u201cWe created our own photoacoustic spectrometer to assess and optimise the probes.\u201d<\/p>\n\n\n\n<p>\u201cThis allowed us to evaluate and characterise the different probes we made to assess a few things,\u201d Deo said. \u201cDid they produce a detectable photoacoustic signal? Are they sensitive enough? That\u2019s how we inferred the next steps.\u201d<\/p>\n\n\n\n<p>But just producing probes that work in a vial wasn\u2019t where the researchers wanted to stop. They then wanted to see how the probes worked in practice. They figured out a way to deliver the probes into a mouse brain and successfully detected photoacoustic signals from neurons inside the targeted brain regions.<\/p>\n\n\n\n<p>\u201cWhile we are excited about the progress, we need to be clear that this is just the first generation of these probes,\u201d Deo said. \u201cWhile they offer a very promising approach, we have a lot more work to do, but it\u2019s a good first demonstration of what this system can enable and the potential it has in better understanding brain function.\u201d<\/p>\n\n\n\n<p>In fact, those next steps include improving the dye delivery system and confirming the ability to use them for dynamic imaging inside cells.<\/p>\n\n\n\n<p>\u201cIt is really one of the advantages of EMBL that it brings together so many people with different kinds of expertise,\u201d Prevedel said. \u201cWe\u2019re both developers in our own way \u2013 my group works more on instrumentation, and Claire\u2019s group does more molecular tools. And combining this with neuroscientists who then truly test the tools \u2013 this is a special and unique way of doing research, only possible at EMBL.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL scientists applied molecular engineering to build photoacoustic probes to label and visualise neurons deep within brain tissue.<\/p>\n","protected":false},"author":100,"featured_media":69923,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591],"tags":[595,18619,1020,43,79,13928,5616,464,704],"embl_taxonomy":[19197,19357],"class_list":["post-69913","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","tag-brain","tag-deep-tissue-imaging","tag-deo","tag-heidelberg","tag-microscopy","tag-neurons","tag-photoacoustics","tag-prevedel","tag-proteins","embl_taxonomy-deo-group-visiting","embl_taxonomy-prevedel-group"],"acf":{"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>New photoacoustic probes enable deep brain tissue imaging, with the potential to report on neuronal activity and enable better understanding of brain function<\/p>\n","related_links":[{"link_description":"Spotlight: Using light and sound to see into the brain","link_url":"https:\/\/www.embl.org\/news\/picture-of-the-week\/spotlight-using-light-and-sound-to-see-into-the-brain\/"}],"source_article":[{"publication_title":"Chemigenetic Far-Red Labels and Ca2+ Indicators Optimized for Photoacoustic Imaging","publication_link":{"title":"","url":"https:\/\/doi.org\/10.1021\/jacs.4c07080","target":""},"publication_authors":"Cook A., Kaydanov N., et al. ","publication_source":"Journal of American Chemical Society","publication_date":"19 August 2024","publication_doi":"doi:10.1021\/jacs.4c07080"}],"in_this_article":false,"press_contact":"None","article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"64999cc4-9a7c-4fea-8339-0e2acc990e08\";i:2;s:36:\"03ee7815-7804-4454-9e1b-b2cee356db46\";}","parents":[],"name":["Deo Group (Visiting)"],"slug":"deo-group-visiting","description":"What &gt; Cell biology and biophysics &gt; Deo Group (Visiting)"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"64999cc4-9a7c-4fea-8339-0e2acc990e08\";i:2;s:36:\"22615b4a-0ac4-4141-8574-199436bb4913\";}","parents":[],"name":["Prevedel Group"],"slug":"prevedel-group","description":"What &gt; Cell biology and biophysics &gt; Prevedel Group"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Seeing into the depths | EMBL<\/title>\n<meta name=\"description\" content=\"EMBL scientists applied molecular engineering to build photoacoustic probes to label and visualise neurons deep within brain tissue.\" \/>\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-technology\/seeing-into-the-depths\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Seeing into the depths | EMBL\" \/>\n<meta property=\"og:description\" content=\"EMBL scientists applied molecular engineering to build photoacoustic probes to label and visualise neurons deep within brain tissue.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science-technology\/seeing-into-the-depths\/\" \/>\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=\"2024-08-27T11:45:19+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-08-27T11:55:57+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/08\/20240731_JACS_Prevedel_final_v2-wp.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1000\" \/>\n\t<meta property=\"og:image:height\" content=\"600\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Ivy Kupec\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@embl\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Ivy Kupec\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"4 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-technology\/seeing-into-the-depths\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/seeing-into-the-depths\/\"},\"author\":{\"name\":\"Ivy Kupec\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/427f2c9b624bc32ffa67d80414712274\"},\"headline\":\"Seeing into the depths\",\"datePublished\":\"2024-08-27T11:45:19+00:00\",\"dateModified\":\"2024-08-27T11:55:57+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/seeing-into-the-depths\/\"},\"wordCount\":735,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science-technology\/seeing-into-the-depths\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2024\/08\/20240731_JACS_Prevedel_final_v2-wp.jpg\",\"keywords\":[\"brain\",\"deep-tissue imaging\",\"deo\",\"heidelberg\",\"microscopy\",\"neurons\",\"photoacoustics\",\"prevedel\",\"proteins\"],\"articleSection\":[\"Science &amp; 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