{"id":10448,"date":"2021-05-10T08:26:30","date_gmt":"2021-05-10T12:26:30","guid":{"rendered":"https:\/\/www.med.unc.edu\/genetics\/?p=10448"},"modified":"2021-05-10T08:27:34","modified_gmt":"2021-05-10T12:27:34","slug":"with-8-million-grant-researchers-aim-to-better-understand-disease-mechanisms-of-schizophrenia","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/genetics\/with-8-million-grant-researchers-aim-to-better-understand-disease-mechanisms-of-schizophrenia\/","title":{"rendered":"With $8-million Grant, Researchers Aim to Better Understand Disease Mechanisms of Schizophrenia"},"content":{"rendered":"

Researchers from the Duke Center for Genomic and Computational Biology, UNC\u2019s Department of Genetics, and Yale University have teamed up to narrow down areas of the genome previously marked relevant to schizophrenia risk.<\/p>\n

\n
\"Patrick
Patrick F. Sullivan, PhD<\/figcaption><\/figure>\n

A new $8-million NIH grant seeks to uncover more clues into what genes increase the risk of developing schizophrenia.<\/p>\n

Greg Crawford, Charlie Gersbach, Tim Reddy and Raluca Gord\u00e2n from the Duke Center for Genomic and Computational Biology have teamed up with Patrick Sullivan, Yun Li, Michael Love, and Paola Giusti-Rodriguez at UNC-Chapel Hill and Flora Vaccarino at Yale University to narrow down areas of the genome previously marked relevant to schizophrenia risk.<\/p>\n

\u201cSchizophrenia is incredibly complex at every level,\u201d Sullivan said, \u201cfrom DNA to its clinical manifestations.\u201d<\/p>\n

Previous genetic studies \u2013some piloted by Sullivan \u2013 have narrowed down the search space. Using samples from 25,000 patients who had schizophrenia and 97,000 samples from those who didn\u2019t, researchers discovered 270 different regions of interest in the genome. These regions vary in size, but each on average span hundreds of thousands of base pairs.<\/p>\n

\u201cBut there\u2019s still a lot we don\u2019t know,\u201d Crawford added. \u201cWe don\u2019t know that within each of these regions, which are the most important parts that confer schizophrenia risk, and what the target genes are.\u201d Other mysteries include how genetic differences manifest themselves, and if all or some of those 270 regions are working together.<\/p>\n

\"SullivanLiLoveGiustiRodriguez\"With this grant, the team will work to narrow down each of those 270 regions to their most important parts. One tactic they will use is high throughput CRISPR screens to silence and\/or activate any region of interest in the genome to see which subregions respond and how. This builds upon nearly 10 years of research between Gersbach and Crawford who have previously collaborated to use CRISPR to regulate human genes in their natural position genome, perturb distal gene regulatory elements in non-coding regions, and scale their efforts up to high throughput screening of hundreds of elements on single genes.<\/p>\n

\u201cNow we are continuing to expand the scale and scope of this work,\u201d Gersbach said, \u201cby assessing thousands of elements on hundreds of genes and applying that to decipher complex disease mechanisms that were previously intractable with a focus on schizophrenia.\u201d<\/p>\n

The team will also take those important regions and use stem cells derived from individuals both with and without schizophrenia and make brain organoids \u2013 cells in a dish that recapitulate different cells in the brain \u2013 and conduct experiments to see what happens if they silence specific regions of the genome.<\/p>\n

Through these efforts, they hope to better understand the basic \u201cparts list\u201d for schizophrenia with greater rigor and certainty than ever before. \u201cWe aren\u2019t going to solve everything,\u201d Crawford said, \u201cbut we will be able to get a better understanding of what\u2019s going on in each of those 270 regions.\u201d<\/p>\n

 <\/p>\n

Article originally posted here: https:\/\/news.unchealthcare.org\/2021\/05\/8m-grant-aims-to-better-understand-disease-mechanisms-of-schizophrenia\/<\/a><\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers from the Duke Center for Genomic and Computational Biology, UNC\u2019s Department of Genetics, and Yale University have teamed up to narrow down areas of the genome previously marked relevant to schizophrenia risk.<\/p>\n","protected":false},"author":28418,"featured_media":10449,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[80,56,34,55],"class_list":["post-10448","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-giusti-rodriguez","tag-li","tag-love","tag-sullivan","odd"],"acf":[],"yoast_head":"\nWith $8-million Grant, Researchers Aim to Better Understand Disease Mechanisms of Schizophrenia | Department of Genetics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" 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