{"id":3646,"date":"2015-04-02T16:14:06","date_gmt":"2015-04-02T14:14:06","guid":{"rendered":"http:\/\/news.embl.de\/?p=3646"},"modified":"2024-11-29T16:54:19","modified_gmt":"2024-11-29T15:54:19","slug":"1504-team-genome","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1504-team-genome\/","title":{"rendered":"Team spirit in the genome"},"content":{"rendered":"\n<p>That\u2019s why understanding genetic predispositions remains a challenge \u2013 each person\u2019s genome is a unique combination of genes, and it\u2019s difficult to work out how they will interact and function as a team. In football, a team of star players may end up standing in each other\u2019s way, whereas a team with good team spirits can achieve success that one might&nbsp;not expect from the players individually.<\/p>\n\n\n\n<p>For the past 100 years geneticists have tried to untangle the complex webs of genetic interactions, and to identify how gene variants affect what other genes do. Ideally, biologists would like a global picture of all genetic interactions in the cell, but this has been hard to track down. Now work led by Michael Boutros of the German Cancer Research Centre (DKFZ), Heidelberg, in collaboration with <a title=\"Huber group\" href=\"http:\/\/www.embl.de\/research\/units\/genome_biology\/huber\/index.html\" target=\"_blank\" rel=\"noopener noreferrer\">Wolfgang Huber<\/a> at EMBL Heidelberg, has shown how it can be done. The study is reported today in the journal <em>eLife<\/em>.<\/p>\n\n\n\n<p>The team developed their approach using cells from the fruit fly <em>Drosophila<\/em>. First they selected genes which, when mutated, had an effect on important characteristics like cell growth and division. This generated a list of 1367 genes, of which 72 were picked out as likely hubs in the genes\u2019 social network.<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-image alignnone size-full wp-image-3650\"><img loading=\"lazy\" decoding=\"async\" width=\"620\" height=\"427\" class=\"vf-figure__image\" src=\"http:\/\/news.embl.de\/wp-content\/uploads\/2015\/04\/1504-huber-1.jpg\" alt=\"Genetic interaction network analysis identifies protein complexes and other groups of closely cooperating proteins (colored dots). Directed interactions of proteins or, or whole groups, with each other are shown with the arrows. For details, please refer to Figure 3 in the article. Credit: EMBL\/DKFZ\" class=\"wp-image-3650\" srcset=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2015\/04\/1504-huber-1.jpg 620w, https:\/\/www.embl.org\/news\/wp-content\/uploads\/2015\/04\/1504-huber-1-300x207.jpg 300w\" sizes=\"auto, (max-width: 620px) 100vw, 620px\" \/><figcaption class=\"vf-figure__caption\">Genetic interaction network analysis identifies protein complexes and other groups of closely cooperating proteins (colored dots). Directed interactions of proteins or, or whole groups, with each other are shown with the arrows. For details, please refer to Figure 3 in the article.&nbsp;Credit: EMBL\/DKFZ<\/figcaption><\/figure>\n\n\n\n<p>To work out which of these genes \u2013 or, more precisely, the proteins they produce \u2013 interact, the team set about silencing pairs of genes using a technique called RNA interference (RNAi). The logic behind this approach is that if the effect of silencing both genes at the same time is different from what is expected from the effects of silencing each of them singularly, then that points to a genetic interaction. In these RNAi experiments, each of the 1367 genes was silenced in combination with one of the 72 key genes. \u201cWe took more than a million images of cells\u201d, says co-author Thomas Sandmann of DKFZ, \u201cand tested almost 100 000 pairwise combinations of silenced genes.\u201d All this data was analysed with automated algorithms on a bank of computers, a process that Bernd Fischer, formerly a member of the Huber lab and now at DKFZ, says \u201cwould have taken more than two years on a single computer\u201d.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>We took more than a million images of cells and tested almost 100 000 pairwise combinations of silenced genes<\/p><\/blockquote>\n\n\n\n<p>Thirteen per cent&nbsp;(12,361) of the pairs showed evidence of a genetic interaction, indicating that they work together. But Fischer and his co-workers weren\u2019t just content knowing which genes interact \u2013 they wanted to know how. So they developed a method to work out the direction of genetic interactions \u2013 whether gene A influenced gene B, or vice versa. \u201cThis is novel, and hasn\u2019t been done on this scale before,\u201d says Huber. Beyond revealing the direction of the interactions, their analysis also showed whether genes amplified, or diminished, the effects of each other. This way of teasing out the way genes interact across the whole cell could be used to shed light on the genetic interactions in many complex cellular processes, from fruit flies to human cells.<\/p>\n\n\n\n<p>Such insights will eventually help towards gaining&nbsp;a better understanding of genomes and their output \u2013 what biologists call the phenotype \u2013 and also for finding new targets for anticancer drugs. Typically, it is difficult to restore the function of proteins that are broken by mutations in cancer, but maps of genetic interactions provide a way around that problem. \u201cNew drugs attempt to exploit lethal genetic interactions to specifically target vulnerabilities in cancer cells,\u201d says Boutros. \u201cAnd genetic interactions may also explain how resistance to cancer drugs arises.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Go Team Genome! New method reveals genetic teamwork in drosophila genome.<\/p>\n","protected":false},"author":12,"featured_media":3648,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[80,478,42,43,49,69],"embl_taxonomy":[],"class_list":["post-3646","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-alumni","tag-drosophila","tag-genomics","tag-heidelberg","tag-interdisciplinary","tag-methods"],"acf":{"article_intro":"<p>Genes, like people, are fundamentally social. Just as we often work in teams, companies, or other more or less complex organisations, genes often work together in genetic networks. And just as our productivity is often influenced by who we work with, the effects of genes depend on the peers they interact with.<\/p>\n","related_links":[{"link_description":" Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ)","link_url":"http:\/\/www.dkfz.de\/signaling\/b110\/Main.html"}],"article_sources":[{"source_description":"<p><span class=\"elife-article-author-item\" style=\"margin: 0px; padding: 0px; border: 0px; outline: 0px; vertical-align: baseline; font-family: inherit; font-size: inherit; font-style: inherit; font-variant: inherit; font-weight: inherit; font-stretch: inherit; line-height: inherit; cursor: pointer; transition: color 0.3s ease-in-out; -webkit-transition: color 0.3s ease-in-out;\" title=\"\" data-tooltip-content=\"|&lt;div class=&quot;author-tooltip&quot;&gt;&lt;div class=&quot;author-tooltip-name&quot;&gt;&lt;span class=&quot;nlm-given-names&quot;&gt;Bernd&lt;\/span&gt; &lt;span class=&quot;nlm-surname&quot;&gt;Fischer&lt;\/span&gt;&lt;\/div&gt;&lt;div class=&quot;author-tooltip-affiliation&quot;&gt;&lt;span class=&quot;author-tooltip-text&quot;&gt;&lt;span class=&quot;nlm-aff&quot;&gt;&lt;span class=&quot;nlm-institution&quot; data-content-type=&quot;dept&quot; data-hwp-id=&quot;institution-1&quot;&gt;Genome Biology Unit&lt;\/span&gt;, &lt;span class=&quot;nlm-institution&quot; data-hwp-id=&quot;institution-2&quot;&gt;European Molecular Biology Laboratory&lt;\/span&gt;, &lt;span class=&quot;nlm-addr-line&quot;&gt;&lt;span class=&quot;nlm-named-content&quot; data-content-type=&quot;city&quot; data-hwp-id=&quot;named-content-1&quot;&gt;Heidelberg&lt;\/span&gt;&lt;\/span&gt;, &lt;span class=&quot;nlm-country&quot;&gt;Germany&lt;\/span&gt;&lt;\/span&gt;&lt;\/span&gt;&lt;\/div&gt;&lt;div class=&quot;author-tooltip-conflict&quot;&gt;&lt;span class=&quot;author-tooltip-text&quot;&gt;&lt;i&gt;No competing interests declared&lt;\/i&gt;&lt;\/span&gt;&lt;\/div&gt;&lt;\/div&gt;\" data-author-inst=\"EuropeanMolecularBiologyLaboratoryGermany\"><span class=\"nlm-given-names\">Bernd<\/span> <span class=\"nlm-surname\">Fischer <em>et al. eLife<\/em>, 6 March 2015.\u00a0<\/span><\/span>DOI: http:\/\/dx.doi.org\/10.7554\/eLife.05464<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.7554\/eLife.05464"}],"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>Team spirit in the genome | EMBL<\/title>\n<meta name=\"description\" content=\"Go Team Genome! 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