{"id":201880,"date":"2025-09-05T08:54:09","date_gmt":"2025-09-05T08:54:09","guid":{"rendered":"https:\/\/www.europesays.com\/us\/201880\/"},"modified":"2025-09-05T08:54:09","modified_gmt":"2025-09-05T08:54:09","slug":"stress-responsive-autophagy-signals-identified-via-crispr","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/201880\/","title":{"rendered":"Stress-Responsive Autophagy Signals Identified via CRISPR"},"content":{"rendered":"

external link<\/a>, co-authored this study. His expertise in genetic screening was instrumental in adapting the screening methodology for this research. His interest in the subject is deeply connected to his work on neurodegenerative diseases, with a particular focus on the autophagy defects characteristic of these conditions.<\/p>\n

Together, their objective was to establish a comprehensive framework and resource to advance fundamental scientific understanding and open new avenues for therapeutic interventions.<\/p>\n

Ambitious use of cutting-edge technology<\/p>\n

To address this challenge, the team conducted kinome-wide CRISPR screens to pinpoint distinct signaling pathways that govern various forms of autophagy. A kinome-wide CRISPR screen employs pooled screening technology to systematically investigate the function of protein kinases\u2014a key family of proteins that regulate numerous cellular processes.<\/p>\n

Dr. Russell notes that kinases are particularly attractive for drug development due to their high level of \u201cdruggability,\u201d making them frequent targets for therapeutic interventions.<\/p>\n

Truc Losier, a joint PhD student in the Rousseaux and Russell labs, developed a new workflow tailored to enable the comparative pathway mapping envisioned by the researchers. While traditional CRISPR screening can survey the whole genome and uncover novel genes and pathways, employing multiple parallel screens streamlines the process of validating targets.<\/p>\n

According to Dr. Russell, the team\u2019s novel methodology incorporated four or five genetic screens simultaneously.<\/p>\n

By integrating results from these multiple datasets, the researchers were able to perform direct, organelle-specific comparisons. This approach\u2014meticulously implemented by Losier\u2014involved generating large pools of genetically altered cells and subjecting them to brief, intense stress conditions lasting only about three to six hours, as opposed to the conventional seven-day protocol, capturing the early phases of autophagy.<\/p>\n

Dr. Russell describes the scale and precision of Losier\u2019s work as exceptionally ambitious, with \u201ca huge breadth of analysis in a very acute window.\u201d The study revealed a scope of unique regulatory mechanisms not previously observed in autophagy research.<\/p>\n

Beyond advancing understanding of autophagy itself, the customized screening strategy developed by the team holds promise for investigators across disciplines who rely on integrated datasets and rapid response experiments. Dr. Russell emphasizes the broader impact of this innovative approach for researchers exploring complex cellular processes, underscoring his lab\u2019s commitment to uncovering the dynamics of autophagy regulation in healthy and pathological tissues.<\/p>\n

The GEM core \u2013 rising to the research challenge<\/p>\n

The team\u2019s hard-won screening methodology was accomplished through an innovative core at the Faculty of Medicine:\u00a0The\u00a0Genome editing and molecular biology (GEM) Facility<\/a>. This uOttawa core facility provides access\u00a0to cutting-edge genetic editing techniques and cDNA cloning.<\/p>\n

\u201cThis was the first screen that came out of this core facility. We have a new genome editing facility where we\u2019re pushing the boundaries of what can be done technically,\u201d says Dr. Russell, who is co-director of the GEM core alongside Dr. Rousseaux.<\/p>\n

Armed with new knowledge from this paper, a next step for the uOttawa team is to\u00a0explore whether they can use the kinases and signaling pathways they discovered to perhaps regulate innate immunity.<\/p>\n

\u201cWe\u2019d like to see if we can pharmacologically regulate pathogen infection using some of those kinases,\u201d Dr. Russell says.<\/p>\n

Reference:\u00a0<\/b>Losier TT, King KE, Rousseaux MWC, Russell RC. Identification of organelle-specific autophagy regulators from tandem CRISPR screens. J Cell Biol. 2025;224(10):e202405138. doi:\u00a010.1083\/jcb.202405138<\/a><\/p>\n

This article has been republished from the following materials<\/a>. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"external link, co-authored this study. His expertise in genetic screening was instrumental in adapting the screening methodology for…\n","protected":false},"author":3,"featured_media":201881,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[815,159,67,132,68],"class_list":{"0":"post-201880","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-united-states","11":"tag-unitedstates","12":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115150852211439740","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/201880","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=201880"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/201880\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/201881"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=201880"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=201880"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=201880"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}