@article {Chowdhury1902, author = {Md. Miraj Kobad Chowdhury and Priyanka Anujan and Lynne Bingle and Colin Bingle}, title = {PIERCEing ciliogenesis: defining a role for PIERCE1 and its{\textquoteright} paralog C15ORF65 in multiciliogenesis}, volume = {56}, number = {suppl 64}, elocation-id = {1902}, year = {2020}, doi = {10.1183/13993003.congress-2020.1902}, publisher = {European Respiratory Society}, abstract = {Cilia are microtubule-based hair-like appendages found on the apical surface of all mammalian cells. Multiciliated cells are found throughout the respiratory tract and defects in cilia function underpins many pulmonary diseases. Many aspects of multiciliogenesis remain to be fully elucidated. Previous studies suggested that Pierce1 is expressed in ciliated cells, upregulated during ciliogenesis, and down-regulated during rhinoviral infection. Mice and zebrafish deficient in pierce1 have cilia defects and exhibit left-right asymmetry. To date no studies have associated C15ORF65, an uncharacterised, divergent paralog of PIERCE1, with ciliogenesis. We hypothesized that PIERCE1 and C15ORF65 are associated with cilia formation and their loss (either alone or in combination) may cause ciliary defects. The objective of our studies is to define the functions of PIERCE1 and C15ORF65 in ciliogenesis. Microarray analysis shows Pierce1 was increased by 13-29 fold as murine nasal, middle ear, and tracheal epithelium underwent mucociliary differentiation. C15orf65 was up-regulated 6-fold in these same epithelia. Similar data was seen in differentiating hBECs. Expression of both genes was observed in HBEC3-KT cells undergoing mucociliary differentiation in culture. To specifically address the role of these proteins in ciliogenesis, PIERCE1 and C15ORF65, were disrupted in HBEC3-KT cells using CRISPR-Cas9 approach. These cells represent unique tools to unravel the role of these proteins in ciliogenesis and we are currently undertaking qualitative and quantitative analysis of these lines.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 1902.This abstract was presented at the 2020 ERS International Congress, in session {\textquotedblleft}Respiratory viruses in the "pre COVID-19" era{\textquotedblright}.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).}, issn = {0903-1936}, URL = {https://erj.ersjournals.com/content/56/suppl_64/1902}, eprint = {https://erj.ersjournals.com/content}, journal = {European Respiratory Journal} }