{"id":24435,"date":"2019-10-03T09:56:12","date_gmt":"2019-10-03T16:56:12","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=24435"},"modified":"2019-10-03T13:26:39","modified_gmt":"2019-10-03T20:26:39","slug":"salk-scientists-find-way-to-quantify-how-well-cutting-edge-microscopy-technique-works","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/salk-scientists-find-way-to-quantify-how-well-cutting-edge-microscopy-technique-works\/","title":{"rendered":"Salk scientists find way to quantify how well cutting-edge microscopy technique works"},"content":{"rendered":"

LA JOLLA\u2014In 2017, Salk scientists reported that tilting a frozen protein sample<\/a> as it sat under an electron microscope was an effective approach to acquiring better information about its structure and helping researchers understand a host of diseases ranging from HIV to cancer. Now, they have developed a mathematical framework that underlies some of those initial observations.<\/p>\n

Their new study, published in Progress in Biophysics and Molecular Biology<\/em><\/a> on September 13, 2019, provides a foundation for quantitatively determining how differences in viewing angles affect the resulting 3D structures of proteins, and could help other researchers determine the best setup for experiments to improve the imaging technique called cryo-EM.<\/p>\n

\"From
From left: Philip Baldwin and Dmitry Lyumkis.<\/p>\n

Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n

Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n

\u201cThis provides a quantitative understanding for why variations in viewing angles affect the quality of resulting 3D structures of proteins, and where we could do better to improve the data,\u201d says Dmitry Lyumkis<\/a>, a Salk assistant professor of genetics and coauthor of the new work. \u201cThese kinds of theoretical frameworks are important to understanding precisely how information is attenuated due to imperfections associated with the imaging experiment, which will lead us to eventually get better structures out of cryo-EM data.\u201d<\/p>\n

In cryo-EM, or cryogenic electron microscopy, proteins are rapidly frozen in their natural form before being bombarded with electrons. By detecting how the electrons scatter when they hit the sample, researchers can determine the molecular structure of the protein or protein complex. Compared to other imaging methods, it\u2019s easier for scientists to prepare proteins for cryo-EM, and the technique can potentially address a broader set of questions in structural biology. However, a long-standing problem in cryo-EM is that proteins tend to stick to the top or bottom of the sample grid that they\u2019re prepared on. These select orientations mean that researchers can\u2019t always see a protein\u2019s structure from every angle. Tilting the sample, Lyumkis and his colleagues found in 2017, helped solve this problem.<\/p>\n

\u201cWe knew that qualitatively, tilting improved the data in some cases,\u201d says Lyumkis. \u201cWhat we didn\u2019t know was exactly the extent to which the structures can be affected by variations in the viewing angle.\u201d<\/p>\n

Recently, Philip Baldwin, a senior staff researcher at Salk and the paper\u2019s coauthor, was examining a set of cryo-EM data collected at different viewing angles when he noticed that such variations affected the overall resolution of the resulting protein structure. After some calculations, he realized that the association between the viewing angle and resolution was generalizable to all cryo-EM experiments.<\/p>\n

The new formula lets researchers calculate, for any protein at any tilt angle, a number called the sampling compensation factor, or SCF. The closer the SCF value is to 1, the more complete the protein\u2019s structure. If the SCF is 0.5 instead of 1, either the data is incomplete, or researchers must collect data for twice as long to get the same structural resolution. By calculating SCF values ahead of an experiment, scientists can optimize their tilt angle and data collection time.<\/p>\n

The new quantitative formulations also helped Lyumkis and Baldwin compute just how incomplete some cryo-EM datasets are. Previously, they might have had to eyeball a set of data and guess whether it was a good or bad approximation of a protein\u2019s structure. Now, the SCF can tell them that numerically.<\/p>\n

\u201cIt\u2019s very handy,\u201d says Baldwin. \u201cBasically, this formula tells you if you have very bad regions of the protein from which you didn\u2019t collect data.\u201d<\/p>\n

Lyumkis and Baldwin hope that using the formula to assess cryo-EM results\u2014which involves a simple calculation or piece of code\u2014will become standard and help guide experiments and new approaches to cryo-EM. This would lead to faster discoveries in basic biological sciences and in drug development.<\/p>\n

The work reflects a growing trend at both the Salk Institute and elsewhere toward integrating computational approaches into biology research.<\/p>\n

Lyumkis and Baldwin were supported by grants from the National Institutes of Health.<\/p>\n

Acerca de Progress in Biophysics & Molecular Biology<\/em>:<\/strong><\/p>\n

Progress in Biophysics & Molecular Biology<\/em>\u00a0an international review journal, covers the ground between the physical and biological sciences. It indicates to the physicist the great variety of unsolved problems awaiting attention in biology and medicine.<\/p>\n

Acerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong><\/p>\n

Every cure has a starting point. The Salk Institute embodies Jonas Salk\u2019s mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer\u2019s, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.<\/p>","protected":false},"featured_media":24436,"template":"","faculty":[320],"disease-research":[333],"class_list":["post-24435","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-dmitry-lyumkis","disease-research-genetics"],"acf":[],"yoast_head":"\nSalk scientists find way to quantify how well cutting-edge microscopy technique works - Salk Institute for Biological Studies<\/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.salk.edu\/es\/news-release\/salk-scientists-find-way-to-quantify-how-well-cutting-edge-microscopy-technique-works\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salk scientists find way to quantify how well cutting-edge microscopy technique works - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014In 2017, Salk scientists reported that tilting a frozen protein sample as it sat under an electron microscope was an effective approach to acquiring better information about its structure and helping researchers understand a host of diseases ranging from HIV to cancer. 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