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You searched for +publisher:"University of Alabama – Birmingham" +contributor:("Bell, P. Darwin<br>"). Showing records 1 – 2 of 2 total matches.

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1. Williams, Corey L. Analysis of cystic kidney disease-related genes in Caenorhabditis elegans.

Degree: PhD, 2009, University of Alabama – Birmingham

Cilia are evolutionarily conserved, membrane-bound, microtubule-based organelles found on a diverse array of cell types in eukaryotic organisms. Inherited diseases of cilia protein dysfunction include Nephronophthisis (NPHP), Joubert Syndrome (JBTS), Meckel-Gruber Syndrome (MKS), and Bardet-Biedl Syndrome (BBS). Important insight in the basic cell biological functions of BBS and NPHP proteins has been gained from analysis in the nematode Caenorhabditis elegans. My goal in this dissertation was to model MKS protein function in cilia biology utilizing the powerful genetic malleability of C. elegans. mks-1 and mks-3, the C. elegans homologs of two MKS-associated proteins in humans, were selected for this analysis. MKS-3 is a transmembrane protein of unknown function, and MKS-1 is a protein comprised of an uncharacterized motif called the B9 domain. Because the B9 domain is found in only two other proteins in C. elegans (and most other eukaryotes), the B9 proteins TZA-1 and TZA-2 were also included in this analysis. Lastly, the C. elegans homologs of NPHP proteins NPHP-1 and NPHP-4 were also analyzed in conjunction with the MKS/TZA proteins. Utilizing mutations in each of the genes encoding these proteins, we were able to develop a model in which the MKS/B9 proteins and the NPHP proteins form independent but functionally related complexes at the base of C. elegans cilia. Disruption of either complex alone by genetic mutation did not hinder cilia formation. However, simultaneous disruption of both complexes resulted in severe ciliogenesis defects. This functional requirement of either the MKS/B9 or the NPHP complex for cilia formation indicates that the two protein complexes serve similar yet distinct roles in maintaining cilia homeostasis. In the absence of a functional MKS/B9 complex, transmembrane proteins that normally localized only to the base of cilia (or just outside of the ciliary base) freely accessed the entire ciliary membrane. This data supports a model in which the MKS/B9 complex regulates ciliary membrane composition by selectively holding some transmembrane proteins at the base of cilia while blocking other transmembrane proteins from accessing the cilium. Overall, this dissertation provides insight into the related but distinct functions of MKS/B9 and NPHP proteins in cilia biology.

xv, 161 p. : ill., digital, PDF file

Cell Biology

Joint Health Sciences

Basal Body Cilia MKS NPHP C. elegans Transition Zone

UNRESTRICTED

Advisors/Committee Members: Miller, Michael A., Yoder, Bradley K.<br>Bell, P. Darwin<br>Marques, Guillero<br>Schwiebert, Erik M.<br>Sztul, Elizabeth S..

Subjects/Keywords: Caenorhabditis elegans  – cytology<; br>; Caenorhabditis elegans  – metabolism<; br>; Caenorhabditis elegans Proteins  – metabolism<; br>; Cilia  – metabolism<; br>; Protein Transport

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Williams, C. L. (2009). Analysis of cystic kidney disease-related genes in Caenorhabditis elegans. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,407

Chicago Manual of Style (16th Edition):

Williams, Corey L. “Analysis of cystic kidney disease-related genes in Caenorhabditis elegans.” 2009. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 12, 2019. http://contentdm.mhsl.uab.edu/u?/etd,407.

MLA Handbook (7th Edition):

Williams, Corey L. “Analysis of cystic kidney disease-related genes in Caenorhabditis elegans.” 2009. Web. 12 Nov 2019.

Vancouver:

Williams CL. Analysis of cystic kidney disease-related genes in Caenorhabditis elegans. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2009. [cited 2019 Nov 12]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,407.

Council of Science Editors:

Williams CL. Analysis of cystic kidney disease-related genes in Caenorhabditis elegans. [Doctoral Dissertation]. University of Alabama – Birmingham; 2009. Available from: http://contentdm.mhsl.uab.edu/u?/etd,407

2. Davenport, James Robert. The role of the primary cilium in energy and glucose metabolism.

Degree: PhD, 2007, University of Alabama – Birmingham

Virtually ignored for years as a useless organelle, the primary cilium has emerged as an essential signaling center in both development and maintenance of tissues in the mammal. The construction and maintenance of the cilium is dependent on intraflagellar transport, a trafficking process where motorized rafts transport essential cargo from the base of the cilium to the tip and then transition back with different motor components to return to the base. Null mutations in intraflagellar transport proteins result in embryonic lethality within mice; although hypomorphic mutations in intraflagellar raft proteins such as Tg737 allow for limited viability with severe pathologies in several organs, most notably cystic renal disease. This dissertation details a thorough analysis of the exocrine and endocrine pancreas pathology demonstrated in the hypomorphic Tg737orpk mutant. These mice display an exocrine phenotype similar to both pancreatitis and the early stages of polycystic pancreatic disease. Tg737orpk embryonic mutants display no histological pathologies, but at birth develop pathogenic “halos” surrounding their zymogen granules that coincide with an increased level of activated carboxypeptidase, unusual increases in acinar cell apoptosis and necrosis leading to atrophy, dilatation of pancreatic ducts, and the deposition of interstitial fibrosis. Tg737orpk mice also display glucose tolerance defects at two weeks of age. In the attempt to elicit the same pathology in adult mice with systemic conditional disruption of IFT components Kif3a and Tg737, we instead discovered a novel hyperphagia-induced obese phenotype in mice. This model was characterized by hyperleptinemia, hyperinsulinemia, hyperglycemia, hepatic steatosis, and slow onset renal and hepatic cystic disease, yet no exocrine pancreas defects. This contrasted the phenotypes seen in the tamoxifen-induced conditional disruption of Tg737 in embryonic mice, which demonstrated a rapid onset renal cystic disease phenotype and no development of obesity. Further tissue-specific conditional disruption found that congenic loss of Kif3a from proopiomelanocortin-expressing cells and Tg737 from differentiated neurons developed hyperphagia-induced obese phenotypes similar to systemic adult disruption of IFT components. Loss of Kif3a in proopiomelanocortin-expressing cells resulted in hyperleptinemia, hyperinsulinemia, hepatic steatosis, and increased linear growth in males similar to the phenotype described in melanocortin pathway mouse mutants. Overall this dissertation demonstrates two novel findings: (1) the role or influence of the primary cilium changes from development to adulthood; and (2) cilia on proopiomelanocortin-expressing neurons are vital in the control of energy metabolism and food intake in the mammal.

xiii, 164 p. : ill., digital, PDF file

Cell Biology

Joint Health Sciences

Cilia Obesity Hyperphagia Insulin Pro-opiomelanocortin Mouse Models

UNRESTRICTED

Advisors/Committee Members: Yoder, Bradley K., Bell, P. Darwin<br>, Kesterson, Robert A.<br>, Nagy, Tim R.<br>, Schwiebert, Erik M..

Subjects/Keywords: Cilia  – metabolism<; br>; Flagella  – metabolism<; br>; Kidney  – metabolism<; br>; Kidney Diseases, Cystic  – metabolism<; br>; Obesity  – metabolism<; br>; Pancreas  – abnormalities<; br>; Pancreas  – pathology<; br>; Tumor Suppressor Proteins

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Davenport, J. R. (2007). The role of the primary cilium in energy and glucose metabolism. (Doctoral Dissertation). University of Alabama – Birmingham. Retrieved from http://contentdm.mhsl.uab.edu/u?/etd,516

Chicago Manual of Style (16th Edition):

Davenport, James Robert. “The role of the primary cilium in energy and glucose metabolism.” 2007. Doctoral Dissertation, University of Alabama – Birmingham. Accessed November 12, 2019. http://contentdm.mhsl.uab.edu/u?/etd,516.

MLA Handbook (7th Edition):

Davenport, James Robert. “The role of the primary cilium in energy and glucose metabolism.” 2007. Web. 12 Nov 2019.

Vancouver:

Davenport JR. The role of the primary cilium in energy and glucose metabolism. [Internet] [Doctoral dissertation]. University of Alabama – Birmingham; 2007. [cited 2019 Nov 12]. Available from: http://contentdm.mhsl.uab.edu/u?/etd,516.

Council of Science Editors:

Davenport JR. The role of the primary cilium in energy and glucose metabolism. [Doctoral Dissertation]. University of Alabama – Birmingham; 2007. Available from: http://contentdm.mhsl.uab.edu/u?/etd,516

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