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Despite the large list of genes linked to this group, which exceeds 80 loci, the number of cellular functions which the gene products engage is relatively limited, among which endoplasmic reticulum (ER) morphogenesis appears central. Mutations in genes encoding ER-shaping proteins are the most common cause of HSP, highlighting the importance of correct ER organisation for long motor neuron survival. However, a major bottleneck in the study of ER morphology is the current lack of quantitative methods, with most studies to date reporting, instead, on qualitative changes. Here, we describe and apply a quantitative image-based screen to identify genetic modifiers of ER organisation using a mammalian cell culture system. An analysis reveals significant quantitative changes in tubular ER and dense sheet ER organisation caused by the siRNA-mediated knockdown of HSP-causing genes ATL1 and RTN2. This screen constitutes the first attempt to examine ER distribution in cells in an automated and high-content manner and to detect genes which impact ER organisation.<\/jats:p>","DOI":"10.3390\/cells13070577","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T13:16:41Z","timestamp":1711459001000},"page":"577","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Automated Imaging-Based Screen for Genetic Modulators of ER Organisation in Cultured Human Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"M. Elena","family":"Garcia-Pardo","sequence":"first","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, 4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7956-7805","authenticated-orcid":false,"given":"Jeremy C.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Cell Screening Laboratory, UCD School of Biology and Environmental Science, University College Dublin, 4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-8145","authenticated-orcid":false,"given":"Niamh C.","family":"O\u2019Sullivan","sequence":"additional","affiliation":[{"name":"UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, 4 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.conb.2018.04.025","article-title":"Converging Cellular Themes for the Hereditary Spastic Paraplegias","volume":"51","author":"Blackstone","year":"2018","journal-title":"Curr. 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