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- W4313172433 abstract "<b>Rationale:</b> In Chronic Obstructive Pulmonary Disease (COPD), the airway epithelium is a site of major pathophysiological change. Genome wide association studies have identified large numbers of genetic variants, potential candidate causal genes and pathways associated with lung function and COPD. However, significant gaps in the functional validation of candidate genes remain. Here, we utilize the genetic amenability of <i>Drosophila melanogaster</i> to conduct a high-throughput, loss-of-function analysis of 65 candidate orthologues in analogous epithelia. <b>Objectives:</b> (i) To complete a primary screen of 65 orthologues in the dorsal thorax epithelium of the fly; (ii) to complete a secondary screen in fly tracheal network, using a subset of genes found to alter epithelial homeostasis; (iii) to translate findings into human bronchial epithelial cell models. <b>Methods:</b> For the primary screen, we combined the MARCM technique and Pannier-Gal4 to generate positively marked, GFP-labelled clones coupled to an RNAi hairpin. Using confocal imaging, epithelial cell and tissue morphogenesis were monitored in real time and knockdown phenotypes scored systematically across 27 distinct categories. <b>Results:</b> Following the completion of our primary screen of 60 genes, we observed several changes in cell shape and behaviour, including apex size, protrusion length, junction integrity and invasion. We have identified INPP5E, ARF4, CYFIP2, and EXOC3 as possible genes of interest so far. <b>Conclusion:</b> Our primary screen has revealed several strong phenotypic ‘hits’ which disrupt epithelial integrity. Ongoing studies aim to carry out parallel investigations in the fly tracheal system and human systems." @default.
- W4313172433 created "2023-01-06" @default.
- W4313172433 creator A5003145893 @default.
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- W4313172433 date "2022-09-04" @default.
- W4313172433 modified "2023-09-26" @default.
- W4313172433 title "An in vivo genetic screen of lung function candidate genes using tissue-specific RNAi in Drosophila melanogaster" @default.
- W4313172433 doi "https://doi.org/10.1183/13993003.congress-2022.1774" @default.
- W4313172433 hasPublicationYear "2022" @default.
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