{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"A Novel Role for Ciliary Proteins in Zymogen Granule Secretion of Pancreatic Acinar Cells","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/76517"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Primary cilia are present on nearly all mammalian cells. For many years, they were thought to be functionless, vestigial organelles. In recent years, primary cilia have been found to be essential for many important biological processes. Included in these are chemo - and mechano-sensation, as well as acting as a signaling hub for hedgehog, Wnt, and notch signaling. Further exemplifying their importance, there is a new classification of genetic disorders, collectively referred to as ciliopathies, which manifest due to aberrant growth and regulation of cilia, and aberrant expression of gene products thought to be critical for these processes. Our lab utilizes a transgenic mouse, which is completely lacking the gene Chibby (Cby). This mutant mouse has been found to have a vast distribution of phenotypes, which overlap with many known ciliopathies. These include chronic sinusitis and otitis, infertility, polycystic kidneys, and pancreatic degeneration. Subsequently, it was found that Cby plays a vital role in ciliogenesis. Of the phenotypes mentioned, the one that has the least mechanistic understanding is pancreatic degeneration. This phenotype has been characterized in a number of other mouse mutants, which have aberrant expression of ciliary genes. The pancreas is composed of two major subclasses, the exocrine and endocrine tissue. The endocrine tissue is composed of the islets of Langerhans, which help to regulate glucose homeostasis. The exocrine tissue is composed mainly of acinar cells, which produce and secrete digestive enzymes in the form of inactive zymogens. These zymogens are secreted apically into the ductal network, where they are transported to the duodenum to aid in proper digestion. All of the endocrine cells, as well as the ductal cells contain primary cilia. The only cells that do not contain primary cilia are the acinar cells. In these ciliopathy mouse models, the cells most deleteriously affected are the acinar cells, which rapidly degenerate after birth. Because of this phenomenon, it has been previously speculated that these cells are degenerating non-cell autonomously. My work has found this not to be the case. I show that acinar cells in Cby mouse models, as well as at least one of these other models, IFT88, are dying cell-autonomously, and these gene products are expressed in acinar cells and play a vital role in proper zymogen vesicle secretion, and in their absence, acinar cells degenerate rapidly due to improper trafficking and secretion. Collectively my work supports growing evidence that ciliary gene products have vital roles outside of the cilium in membrane trafficking, and collectively referring to any phenotype resulting from aberrant expression of these gene products, as a ciliopathy may be na\u00efve."},{"label":"dcterms.available","value":"2017-09-20T16:50:31Z"},{"label":"dcterms.contributor","value":"Brown, Deborah"},{"label":"dcterms.creator","value":"Cyge, Benjamin Sy"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:50:31Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:50:31Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Pharmacology."},{"label":"dcterms.extent","value":"92 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/76517"},{"label":"dcterms.issued","value":"2015-08-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:50:31Z (GMT). No. of bitstreams: 1\nCyge_grad.sunysb_0771E_11990.pdf: 18497193 bytes, checksum: a90ff65da7d6bded54a1f291bb5e5014 (MD5)\n  Previous issue date: 2014"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Cellular biology"},{"label":"dcterms.title","value":"A Novel Role for Ciliary Proteins in Zymogen Granule Secretion of Pancreatic Acinar Cells"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/55%2F81%2F16%2F55811675422131698122176247921665311312/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/55%2F81%2F16%2F55811675422131698122176247921665311312","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}