You searched for subject:(Department of Anatomy AND Cell Biology thesis Ph D mesh ).
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University of Florida
1.
Teng-Umnuay, Patana, 1961-.
Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium.
Degree: 1998, University of Florida
URL: https://ufdc.ufl.edu/AA00025055 
Subjects/Keywords: Amino acids; Chromatography; Enzyme activity; Enzymes; Gels; Ions; pH; Polysaccharides; Purification; Sugars; Carbohydrate Conformation ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Dictyostelium ( mesh ); Glycopeptides ( mesh ); Glycosylation ( mesh ); Polysaccharides ( mesh ); Research ( mesh ); Transferases ( mesh )
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APA (6th Edition):
Teng-Umnuay, Patana, 1. (1998). Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00025055
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Teng-Umnuay, Patana, 1961-. “Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium.” 1998. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00025055.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Teng-Umnuay, Patana, 1961-. “Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium.” 1998. Web. 16 Jan 2021.
Vancouver:
Teng-Umnuay, Patana 1. Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium. [Internet] [Thesis]. University of Florida; 1998. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00025055.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Teng-Umnuay, Patana 1. Structure of a Skp1-glycan and biogenesis of its peptide linkage in Dictyostelium. [Thesis]. University of Florida; 1998. Available from: https://ufdc.ufl.edu/AA00025055
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
2.
Mandell, Robert Barry, 1963-.
Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes.
Degree: 1991, University of Florida
URL: https://ufdc.ufl.edu/AA00009066
Subjects/Keywords: Cytoplasm; Gels; Nuclear membrane; Nuclear pore; Oocytes; Proteins; Rats; Recycling; RNA; Signals; Biological Transport ( mesh ); Cell Nucleus ( mesh ); Cytoplasm ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Heat-Shock Proteins 70 ( mesh ); Oocytes ( mesh ); Research ( mesh ); Xenopus ( mesh )
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APA (6th Edition):
Mandell, Robert Barry, 1. (1991). Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00009066
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mandell, Robert Barry, 1963-. “Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes.” 1991. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00009066.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mandell, Robert Barry, 1963-. “Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes.” 1991. Web. 16 Jan 2021.
Vancouver:
Mandell, Robert Barry 1. Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes. [Internet] [Thesis]. University of Florida; 1991. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00009066.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mandell, Robert Barry 1. Nucleocytoplasmic transport of hsp70-related proteins in Xenopus oocytes. [Thesis]. University of Florida; 1991. Available from: https://ufdc.ufl.edu/AA00009066
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
3.
Gonzalez-Yanes, Beatriz, 1964-.
A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum.
Degree: 1991, University of Florida
URL: https://ufdc.ufl.edu/AA00025763
Subjects/Keywords: Cytosol; Digestion; Enzymes; Gels; Glycopeptides; Glycoproteins; In vitro fertilization; Lectins; Oligosaccharides; Radioactive decay; Cytosol ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Dictyostelium ( mesh ); Fucose ( mesh )
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APA (6th Edition):
Gonzalez-Yanes, Beatriz, 1. (1991). A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00025763
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gonzalez-Yanes, Beatriz, 1964-. “A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum.” 1991. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00025763.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gonzalez-Yanes, Beatriz, 1964-. “A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum.” 1991. Web. 16 Jan 2021.
Vancouver:
Gonzalez-Yanes, Beatriz 1. A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum. [Internet] [Thesis]. University of Florida; 1991. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00025763.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gonzalez-Yanes, Beatriz 1. A novel fucosylation pathway in the cytosol of Dictyostelium Discoideum. [Thesis]. University of Florida; 1991. Available from: https://ufdc.ufl.edu/AA00025763
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
4.
Tuttle, Daniel Lee, 1955-.
Mechanisms of autophagy in methylotrophic yeasts.
Degree: 1995, University of Florida
URL: https://ufdc.ufl.edu/AA00011831
Subjects/Keywords: Alcohols; Enzymes; Ethanol; Nitrogen; Oxidases; Pastors; Peroxisomes; Starvation; Vacuoles; Yeasts; Autophagocytosis – genetics ( mesh ); Autophagocytosis – physiology ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Endopeptidases ( mesh ); Ethanol – physiology ( mesh ); Gene Library ( mesh ); Glucose – physiology ( mesh ); Methanol – physiology ( mesh ); Microbodies – physiology ( mesh ); Models, Biological ( mesh ); Nitrogen – pharmacology ( mesh ); Pichia – anatomy &; histology ( mesh ); Pichia – genetics ( mesh ); Pichia – physiology ( mesh ); Research ( mesh ); Vacuoles – physiology ( mesh )
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APA (6th Edition):
Tuttle, Daniel Lee, 1. (1995). Mechanisms of autophagy in methylotrophic yeasts. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00011831
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Tuttle, Daniel Lee, 1955-. “Mechanisms of autophagy in methylotrophic yeasts.” 1995. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00011831.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tuttle, Daniel Lee, 1955-. “Mechanisms of autophagy in methylotrophic yeasts.” 1995. Web. 16 Jan 2021.
Vancouver:
Tuttle, Daniel Lee 1. Mechanisms of autophagy in methylotrophic yeasts. [Internet] [Thesis]. University of Florida; 1995. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00011831.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tuttle, Daniel Lee 1. Mechanisms of autophagy in methylotrophic yeasts. [Thesis]. University of Florida; 1995. Available from: https://ufdc.ufl.edu/AA00011831
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
5.
Shi, Yujiang, 1968-.
The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.
Degree: 2000, University of Florida
URL: https://ufdc.ufl.edu/AA00054632
Subjects/Keywords: Cadherins; Cancer; Cell adhesion; Cell growth; Cells; Desmoplakins; Desmosomes; Epithelial cells; Epithelium; Tumors; Cell Adhesion Molecules ( mesh ); Cell Cycle ( mesh ); Cell Nucleus – chemistry ( mesh ); Chromosome Mapping ( mesh ); Chromosomes, Human, Pair 14 ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Desmosomes – chemistry ( mesh ); Epithelial Cells ( mesh ); Gene Expression Regulation ( mesh ); Genes, Tumor Suppressor ( mesh ); Neoplasms – genetics ( mesh ); Phosphoproteins ( mesh ); Research ( mesh )
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APA (6th Edition):
Shi, Yujiang, 1. (2000). The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00054632
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shi, Yujiang, 1968-. “The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.” 2000. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00054632.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shi, Yujiang, 1968-. “The Biological function of pinin/DRS/memA and its involvement in tumorigenesis.” 2000. Web. 16 Jan 2021.
Vancouver:
Shi, Yujiang 1. The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. [Internet] [Thesis]. University of Florida; 2000. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00054632.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shi, Yujiang 1. The Biological function of pinin/DRS/memA and its involvement in tumorigenesis. [Thesis]. University of Florida; 2000. Available from: https://ufdc.ufl.edu/AA00054632
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
6.
Fu, Zheng, 1971-.
Characterization of four alternatively spliced casein kinase 1 alpha isoforms.
Degree: 1999, University of Florida
URL: https://ufdc.ufl.edu/AA00029725
Subjects/Keywords: Antibodies; Cells; In vitro fertilization; Phosphatases; Phosphorylation; Protein isoforms; Proteins; Signals; Splicing; Yeasts; Alternative Splicing ( mesh ); Caseins ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Gene Expression Regulation ( mesh ); Neurofilament Proteins ( mesh ); Protein Isoforms ( mesh ); Protein-Serine-Threonine Kinases – genetics ( mesh ); Protein-Serine-Threonine Kinases – isolation &; purification ( mesh )
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APA ·
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APA (6th Edition):
Fu, Zheng, 1. (1999). Characterization of four alternatively spliced casein kinase 1 alpha isoforms. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00029725
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fu, Zheng, 1971-. “Characterization of four alternatively spliced casein kinase 1 alpha isoforms.” 1999. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00029725.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fu, Zheng, 1971-. “Characterization of four alternatively spliced casein kinase 1 alpha isoforms.” 1999. Web. 16 Jan 2021.
Vancouver:
Fu, Zheng 1. Characterization of four alternatively spliced casein kinase 1 alpha isoforms. [Internet] [Thesis]. University of Florida; 1999. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00029725.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fu, Zheng 1. Characterization of four alternatively spliced casein kinase 1 alpha isoforms. [Thesis]. University of Florida; 1999. Available from: https://ufdc.ufl.edu/AA00029725
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
7.
Curtis, Lisa M.
Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology.
Degree: 2001, University of Florida
URL: https://ufdc.ufl.edu/AA00022185
Subjects/Keywords: Antibodies; Apoptosis; Arrows; Cell growth; Cell membranes; Cells; Kidney cortex; Kidneys; Rats; Receptors; Angiotensin II ( mesh ); Apoptosis ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Nephrons – physiology ( mesh ); Proton-Translocating ATPases ( mesh ); rab GTP-Binding Proteins ( mesh )
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APA (6th Edition):
Curtis, L. M. (2001). Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00022185
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Curtis, Lisa M. “Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology.” 2001. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00022185.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Curtis, Lisa M. “Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology.” 2001. Web. 16 Jan 2021.
Vancouver:
Curtis LM. Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology. [Internet] [Thesis]. University of Florida; 2001. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00022185.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Curtis LM. Vacuolar H-ATPase and the nephron developmental apoptosis and adult physiology. [Thesis]. University of Florida; 2001. Available from: https://ufdc.ufl.edu/AA00022185
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
8.
LaFleur, Gary James, 1963-.
Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins.
Degree: 1996, University of Florida
URL: https://ufdc.ufl.edu/AA00025778
Subjects/Keywords: Amino acids; Codons; Complementary DNA; Egg proteins; Generally accepted auditing standards; Liver; Oocytes; Proteins; RNA; Vertebrates; Amino Acid Sequence ( mesh ); Chorion – physiology ( mesh ); DNA, Complementary ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Egg Proteins – chemistry ( mesh ); Egg Proteins – genetics ( mesh ); Estradiol – physiology ( mesh ); Killifishes ( mesh ); Liver – physiology ( mesh ); Ovum – growth &; development ( mesh ); Ovum – physiology ( mesh ); Vitellogenin – chemistry ( mesh ); Vitellogenin – genetics ( mesh )
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APA (6th Edition):
LaFleur, Gary James, 1. (1996). Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00025778
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
LaFleur, Gary James, 1963-. “Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins.” 1996. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00025778.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
LaFleur, Gary James, 1963-. “Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins.” 1996. Web. 16 Jan 2021.
Vancouver:
LaFleur, Gary James 1. Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins. [Internet] [Thesis]. University of Florida; 1996. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00025778.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
LaFleur, Gary James 1. Estrogen-induced hepatic contributions to ovarian follicle development in Fundulus heteroclitus : vitellogenins and choriogenins. [Thesis]. University of Florida; 1996. Available from: https://ufdc.ufl.edu/AA00025778
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Florida
9.
Wu, Pei, 1968-.
Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae.
Degree: 1998, University of Florida
URL: https://ufdc.ufl.edu/AA00054297
Subjects/Keywords: Boxes; Cells; Nuclear proteins; Plasmids; Proteins; Ribosomes; RNA; Small nucleolar ribonucleoproteins; Small nucleolar RNA; Yeasts; Amino Acid Sequence ( mesh ); Cell Nucleolus ( mesh ); Department of Anatomy and Cell Biology thesis Ph.D ( mesh ); Molecular Sequence Data ( mesh ); Nuclear Proteins – chemistry ( mesh ); Nuclear Proteins – genetics ( mesh ); Nuclear Proteins – physiology ( mesh ); RNA Precursors ( mesh ); RNA Processing, Post-Transcriptional ( mesh ); RNA, Ribosomal, 18S ( mesh ); Research ( mesh ); Ribonucleoproteins, Small Nuclear – chemistry ( mesh ); Ribonucleoproteins, Small Nuclear – genetics ( mesh ); Ribonucleoproteins, Small Nuclear – physiology ( mesh ); Ribosomes – metabolism ( mesh ); Saccharomyces cerevisiae ( mesh ); Sequence Homology, Amino Acid ( mesh )
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APA ·
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APA (6th Edition):
Wu, Pei, 1. (1998). Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae. (Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/AA00054297
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wu, Pei, 1968-. “Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae.” 1998. Thesis, University of Florida. Accessed January 16, 2021.
https://ufdc.ufl.edu/AA00054297.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wu, Pei, 1968-. “Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae.” 1998. Web. 16 Jan 2021.
Vancouver:
Wu, Pei 1. Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae. [Internet] [Thesis]. University of Florida; 1998. [cited 2021 Jan 16].
Available from: https://ufdc.ufl.edu/AA00054297.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wu, Pei 1. Identification and characterization of novel nucleolar proteins involved in ribosome biogenesis in Saccharomyces cerevisiae. [Thesis]. University of Florida; 1998. Available from: https://ufdc.ufl.edu/AA00054297
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Arizona
10.
Nye, Jonathan.
Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
.
Degree: 2014, University of Arizona
URL: http://hdl.handle.net/10150/332835
► Centrosomes are complex organelles consisting of a pair of small microtubule based structures called centrioles embedded in an amorphous cloud of pericentriolar material (PCM). These…
(more)
▼ Centrosomes are complex organelles consisting of a pair of small microtubule based structures called centrioles embedded in an amorphous cloud of pericentriolar material (PCM). These organelles are critical for proper mitotic spindle assembly and orientation, and can also migrate to the plasma membrane where, as basal bodies, they serve to nucleate cilia¹. Centrioles are the core duplicating elements of the centrosome and, similar to DNA, duplicate once per
cell cycle during S-phase². Errors in this process can lead to a
cell that contains too many or too few centrosomes and are thought to promote tumorigenesis by directly promoting genomic instability and loss of polarity in stem cells³⁻⁷. Polo-like kinase 4 (Plk4) and Asterless (Asl) are both essential for centriole duplication to occur and overexpression of either of these proteins leads to cells that contain too many centrosomes, a condition known as centrosome amplification. Interestingly, both of these proteins also have the unique ability to promote de novo formation of centrioles in cells that normally lack centrioles⁸⁻¹⁴. Plk4 is a member of the Polo-like kinase family of proteins and is named after the founding member Drosophila Polo¹⁵. In humans, there are four members (Plk1-4) that all share sequence similarity and an N-terminal ser/thr kinase domain. Plk's 1-3 all contain two characteristic Polo box (PB) motifs, downstream of the kinase domain, that consist of a six stranded β-sheet lying across a C-terminal α-helix¹⁶. However, Plk4 was thought to be unique among family members since it only contained one C-terminal PB domain and a larger cryptic polo box domain that showed very little sequence similarity to known PBs. However, we performed an in-depth structure/function analysis of this cryptic polo box region and were able to determine, through x-ray crystallography, that Plk4 is unique among Plk family members not because it contains one PB domain but, in fact, because it contains three polo box domains. Thus, the cryptic polo box domain contains two previously unidentified polo boxes, termed PB1-PB2, upstream of the C-terminal PB3¹⁷. Furthermore, we found that PB1-PB2 is necessary for proper localization of Plk4 and that the entire PB1-PB2 cassette is necessary for binding to Asl. Our results also indicate that the PB1-PB2 domain plays a critical role in regulating Plk4 autophosphorylation and degradation, in order to restrict centriole duplication to once and only once per
cell cycle. Previously Asl has been shown to be not only a binding partner of Plk4 but also a substrate for Plk4 kinase activity, however, the functional significance of this phosphorylation has remained elusive⁹. Our work has shown that Asl phosphorylation by Plk4 is conserved from flies to humans and is restricted to the N-terminal (Asl-A) region. In total we identified 13 phosphorylated residues via mass spectrometry. Analysis of phosphorylation mutant constructs revealed that Plk4 and Asl are involved in a novel feedback loop controlling centriole duplication. This feedback…
Advisors/Committee Members: Rogers, Gregory (advisor), Rogers, Gregory (committeemember), Krieg, Paul (committeemember), Weinert, Ted (committeemember), McDermott, Kimberly (committeemember), Lybarger, Lonnie (committeemember).
Subjects/Keywords: Cell Biology & Anatomy
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APA (6th Edition):
Nye, J. (2014). Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/332835
Chicago Manual of Style (16th Edition):
Nye, Jonathan. “Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
.” 2014. Doctoral Dissertation, University of Arizona. Accessed January 16, 2021.
http://hdl.handle.net/10150/332835.
MLA Handbook (7th Edition):
Nye, Jonathan. “Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
.” 2014. Web. 16 Jan 2021.
Vancouver:
Nye J. Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
. [Internet] [Doctoral dissertation]. University of Arizona; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10150/332835.
Council of Science Editors:
Nye J. Utilizing S2 Cells to Study the Molecular Mechanisms Regulating Centriole Duplication
. [Doctoral Dissertation]. University of Arizona; 2014. Available from: http://hdl.handle.net/10150/332835
University of Arizona
11.
Bhagwandin, Candida B.
The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
.
Degree: 2014, University of Arizona
URL: http://hdl.handle.net/10150/333037
► Membrane-Associated RING-CH1 (MARCH1) is a highly-conserved E3 ubiquitin ligase identified as a potent regulator of the immune modulatory molecules, Major Histocompatibility Complex II (MHC-II), and…
(more)
▼ Membrane-Associated RING-CH1 (MARCH1) is a highly-conserved E3 ubiquitin ligase identified as a potent regulator of the immune modulatory molecules, Major Histocompatibility Complex II (MHC-II), and co-stimulatory molecules (such as CD86). Antigen-presenting cells (APCs), such as dendritic cells, are induced to mature following interaction with stimuli, including microbial ligands and cytokines, whereupon MHC-II and CD86 surface expression is significantly upregulated. At the surface of the APC, these MARCH1 substrates provide signals critical for T
cell activation and induction of the appropriate adaptive immune response. As a key regulator of the T
cell-APC conversation, it is imperative to gain a thorough understanding of the underlying regulatory mechanisms governing MARCH1 expression and function, and the biological consequences of dysregulation of this E3 ligase. Indeed, it has been demonstrated that MARCH1 gene transcription is negatively-regulated upon APC maturation. We have shown that MARCH1 function is regulated at additional levels. We have observed that MARCH1 is rapidly degraded under normal circumstances. Further, its activity also appears to be negatively regulated by APC maturation, possibly through post-translational modifications including phosphorylation. The fact that MARCH1 is
subject to multiple levels of regulation indicates a need for precise control of antigen-presentation. Interestingly, MARCH1-deficient mice on a normal diet show changes in organismal metabolism, which is known to be regulated, in part, by immune cells. We observed gender-associated dimorphisms in weight gain, visceral adipose tissue (VAT) deposits, and increased inflammation of the VAT, all characteristic of insulin-resistance and type II diabetes progression. However, despite exhibiting these hallmark risk factors of metabolic dysregulation, MARCH1-deficient mice show increased glucose tolerance compared to wildtype mice. Collectively, the data support the hypothesis that MARCH1 is stringently regulated to ensure proper control of the adaptive immune response, and suggest a novel role for this E3 ligase in the maintenance of metabolic homeostasis.
Advisors/Committee Members: Lybarger, Lonnie (advisor), Lybarger, Lonnie (committeemember), Krieg, Paul (committeemember), Rogers, Gregory (committeemember), Larmonier, Nicolas (committeemember).
Subjects/Keywords: Cell Biology & Anatomy
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APA (6th Edition):
Bhagwandin, C. B. (2014). The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
. (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/333037
Chicago Manual of Style (16th Edition):
Bhagwandin, Candida B. “The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
.” 2014. Doctoral Dissertation, University of Arizona. Accessed January 16, 2021.
http://hdl.handle.net/10150/333037.
MLA Handbook (7th Edition):
Bhagwandin, Candida B. “The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
.” 2014. Web. 16 Jan 2021.
Vancouver:
Bhagwandin CB. The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
. [Internet] [Doctoral dissertation]. University of Arizona; 2014. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10150/333037.
Council of Science Editors:
Bhagwandin CB. The Regulatory Mechanisms Governing The E3 Ubiquitin Ligase, Membrane-Associated RING-CH1 (MARCH1), And The Consequences Of Dysregulation On Metabolism
. [Doctoral Dissertation]. University of Arizona; 2014. Available from: http://hdl.handle.net/10150/333037
McGill University
12.
Niftullayev, Sadig.
A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons.
Degree: MS, Department of Anatomy and Cell Biology, 2018, McGill University
URL: https://escholarship.mcgill.ca/downloads/73666701n.pdf
;
https://escholarship.mcgill.ca/concern/theses/t722hc16j
► Axon outgrowth and path-finding are crucial points in the development of the Central Nervous System (CNS), where neurons use the distal tip of their axons—…
(more)
▼ Axon outgrowth and path-finding are crucial points in the development of the Central Nervous System (CNS), where neurons use the distal tip of their axons— the growth cone— to navigate towards their final destination. The growth cone contains highly dynamic actin cytoskeleton and it carries the machinery to respond to various guidance cues, one of which is netrin-1— a secreted, laminin-like protein family. Netrin-1 signal through a cell membrane receptor protein— deleted in colorectal cancer (DCC)— to induce an attractive response. Mutations and small nucleotide polymorphisms (SNPs) in different components of netrin-1/DCC signalling pathway have been implicated in neurological disorders such as congenital mirror movement, schizophrenia, Parkinson's disease, aggressive behavior, and Alzheimer's disease. Although our understanding of the netrin-1/DCC signalling pathway is far from complete, work from different research group has strongly hinted at the substantial role of the Rho family of small GTPases downstream of this pathway. Among other functions, small Rho GTPases regulate the dynamics of actin cytoskeleton, which is an important component of the growth cone movement. The activity of small Rho GTPases is regulated by three classes of upstream proteins— Guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), and GDP-dissociation inhibitors (GDIs)— roles of which in axon guidance have been studied only to a limited extent. In the first chapter of this thesis, we have reviewed the classic guidance cues and their receptors, as well as, the role of Rho GTPases and their regulators— GAPs and GEFs— in axon outgrowth and guidance. In this chapter, we have particularly focused on the involvement of GAPs and GEFs in neurological disorders. In the second chapter, we have demonstrated our findings related to the role of p190— a GAP protein that is active towards RhoA— in the development of cortical neurons downstream of netrin-1/DCC signalling pathway. It has already been shown that p190 is an important protein for CNS development as it is involved in fear memory formation, axon outgrowth and guidance; however, its role in netrin-1/DCC pathway has not been addressed yet. In this chapter, we report that p190 forms a complex with RasGAP and DCC in both HEK293 cells and cortical neurons. We have also shown that, in cortical neurons, upon netrin-1 stimulation, p190 is phosphorylated by Src family kinases. We have documented a similar effect in HEK293 cells upon overexpression of DCC. In addition, we have noted that the tyrosine 1418 (Y1418) residue of DCC is crucial for its binding to p190. Furthermore, we observed that p190 is highly expressed in cortical neurons, where it has similar localization patterns with, actin, DCC, and Rho-GTP at the growth cone. Finally, we have reported that along with its SH2 domains, the SH3 domain of p120RasGAP is also interacting with p190. Together, these findings suggest a role for p190 downstream of netrin-1/DCC signalling pathway.
La croissance et le guidage axonal…
Advisors/Committee Members: Nathalie Lamarche (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA (6th Edition):
Niftullayev, S. (2018). A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/73666701n.pdf ; https://escholarship.mcgill.ca/concern/theses/t722hc16j
Chicago Manual of Style (16th Edition):
Niftullayev, Sadig. “A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons.” 2018. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/73666701n.pdf ; https://escholarship.mcgill.ca/concern/theses/t722hc16j.
MLA Handbook (7th Edition):
Niftullayev, Sadig. “A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons.” 2018. Web. 16 Jan 2021.
Vancouver:
Niftullayev S. A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons. [Internet] [Masters thesis]. McGill University; 2018. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/73666701n.pdf ; https://escholarship.mcgill.ca/concern/theses/t722hc16j.
Council of Science Editors:
Niftullayev S. A role for p190RhoGAP in the signaling mechanisms mediated by the axon guidance cue netrin-1 and its receptor deleted in colorectal cancer (DCC) in primary cortical neurons. [Masters Thesis]. McGill University; 2018. Available from: https://escholarship.mcgill.ca/downloads/73666701n.pdf ; https://escholarship.mcgill.ca/concern/theses/t722hc16j
McGill University
13.
Kato, Tatsuya.
Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing.
Degree: MS, Department of Anatomy and Cell Biology, 2018, McGill University
URL: https://escholarship.mcgill.ca/downloads/xw42nb118.pdf
;
https://escholarship.mcgill.ca/concern/theses/zc77ss161
► Introduction: Afin d'assurer leur survie, les cellules doivent être capables de s'adapter à une myriade de forces mécaniques. Elles y arrivent en maintenant les forces…
(more)
▼ Introduction: Afin
d'assurer leur survie, les cellules doivent être capables de s'adapter à une myriade de forces mécaniques. Elles y arrivent en maintenant les forces les affectants dans un état
d'homéostasie dynamique leur conférant un certain degré de stabilité structurelle et est souvent décrite sous l'égide du mot-valise tenségrité. Lorsque qu'une cellule est endommagée, sa tenségrité est interrompue, menant à une augmentation transitoire de la tension autours du dommage cellulaire. La cellule endommagée se doit donc de réparer les dommages faits à sa membrane plasmidique et à son cytosquelette. La réparation du cytosquelette est orchestrée par l'activité coordonné de RhoA et de Cdc42 qui régule la formation et la contraction
d'un anneau
d'actomyosine se formant autour de la "plaie" cellulaire. La formation de cet anneau est reconnu de dépendre principalement del'influx de calcium et les changements de composition lipidique de la membrane plasmidique qui accompagnent les dommages cellulaires. En revanche, la présence
d'une possible relation entre les changements dynamiques de tension ayant lieux au site de dommages cellulaires et la réparation cellulaire médiée par la formation et la contraction
d'un anneau
d'actomyosine reste entièrement inexplorée.Hypothèse: L'augmentation de la tension locale transitoire aux sites de dommage cellulaire est nécessaire pour la réparation cellulaire médiée par la formation et la contraction
d'anneau actomyosine.Méthodes: Afin de diminuer les changements dynamiques de tension ayant lieux au site de dommages cellulaires, des ovocytes de Xenopus laevis furent incubés dans des milieux de cultures hypertoniques. L'efficacité de ces traitements fut ensuite confirmée en mesurant le module
d'élasticité (module de Young) des ovocytes traités et
d'ovocytes contrôles par microindentation. L'impact de la diminution de la tension sur la réparation cellulaire et la formation
d'anneaux
d'actomyosine fut ensuite directement évaluée par microscopie confocale. Les niveaux de RhoA, de Cdc42 furent également évalués par le biais
d'immunotransferts (western blots) et
d'immunoprécipitations.Résultats: Tel qu'attendu, les ovocytes incubés dans les milieux hypertoniques avaient des modules
d'élasticités nettement plus bas que les ovocytes contrôles, ce qui serait compatible avec une diminution de la tension cellulaire dans ces ovocytes. Parallèlement, les ovocytes incubés dans les milieux hypertoniques montraient de sévères lacunes en ce qui concerne la réparation du cytosquelette et avaient des diminutions notables dans l'enrichissement
d'actine et de RhoA actif en périphérie des plaies cellulaires. En revanche, l'accumulation de Cdc42 actif autour de la plaie était inchangée. Nos résultats
d'immunotransferts et
d'immunoprécipitations ont également révélés la présence de niveaux réduits de RhoA actif et des niveaux accrus de Cdc42 actif dans les extraits
d'ovocytes incubés dans les milieux hypertoniques. Conclusions: La présence
d'une augmentation transitoire de tension locale aux sites de dommage…
Advisors/Committee Members: Craig A. Mandato (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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APA (6th Edition):
Kato, T. (2018). Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/xw42nb118.pdf ; https://escholarship.mcgill.ca/concern/theses/zc77ss161
Chicago Manual of Style (16th Edition):
Kato, Tatsuya. “Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing.” 2018. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/xw42nb118.pdf ; https://escholarship.mcgill.ca/concern/theses/zc77ss161.
MLA Handbook (7th Edition):
Kato, Tatsuya. “Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing.” 2018. Web. 16 Jan 2021.
Vancouver:
Kato T. Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing. [Internet] [Masters thesis]. McGill University; 2018. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/xw42nb118.pdf ; https://escholarship.mcgill.ca/concern/theses/zc77ss161.
Council of Science Editors:
Kato T. Tension change of «Xenopus laevis» oocytes influences Rho GTPase regulation of wound healing. [Masters Thesis]. McGill University; 2018. Available from: https://escholarship.mcgill.ca/downloads/xw42nb118.pdf ; https://escholarship.mcgill.ca/concern/theses/zc77ss161
McGill University
14.
Antoine-Bertrand, Judith.
Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC.
Degree: PhD, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/h989r592r.pdf
;
https://escholarship.mcgill.ca/concern/theses/b5644v38n
► In order to reach the exceptional level of interconnectivity observed in the nervous system, newborn neurons must accomplish the feat of establishing appropriate synaptic connections…
(more)
▼ In order to reach the exceptional level of interconnectivity observed in the nervous system, newborn neurons must accomplish the feat of establishing appropriate synaptic connections as they navigate through the plethora of directional cues expressed in the extracellular environment. The distal tip of the axon, called the growth cone, expresses cell surface receptors that sense these extracellular cues and trigger intracellular signaling cascades that direct the growth of the axon. This thesis examines the molecular mechanisms that mediate attractive axon guidance downstream of the chemotropic cue netrin-1 and its receptor deleted in colorectal cancer (DCC). DCC becomes phosphorylated following the binding of netrin-1 to its extracellular domain. Notably, the phosphorylation of the conserved tyrosine residue 1418 (Y1418) is essential for netrin-1 signal transduction in the vertebrate central nervous system. Here, the regulatory function of the Y1418 residue is explored in the context of netrin-1 signal transduction via the characterization of two novel protein interactions with DCC. This thesis demonstrates that upon the binding of netrin-1, Y1418 phosphorylation mediates the recruitment to DCC of ezrin, a member of the actin-binding ezrin-radixin-moesin (ERM) protein family, and of p120RasGAP, a GTPase-activating protein (GAP) for proteins of the Ras subfamily of small GTPases. Both ezrin and p120RasGAP are shown to be required for netrin-1-dependent functions such as axon outgrowth and growth cone attraction. Furthermore, the discovery that the activity of RhoA, a Rho subfamily GTPase, is required downstream of netrin-1 for the phosphorylation of the ERM proteins instigates the assessment of the spatiotemporal regulation of RhoA in response to netrin-1, which results in the detection of previously unreported netrin-1-induced RhoA activity. Taken together, the novel findings presented in this thesis improve our understanding of the signaling cascades that regulate netrin-1/DCC-mediated attractive axon guidance during the development of the nervous system.
L'interconnectivité exceptionnelle des réseaux neuronaux est acquise grâce aux neurones en développement qui doivent relever le défi d'établir des connexions synaptiques adéquates tout en naviguant dans un environnement extracellulaire dans lequel est exprimée une grande variété de molécules-guides. La région distale de l'axone, appelée le cône de croissance, exprime à sa surface des récepteurs qui engendrent des cascades de signalisation intracellulaire qui guide la croissance de l'axone. Cette thèse aborde les mécanismes moléculaires impliqués dans le guidage axonal en aval du facteur chémo-attractif nétrine-1 et de son récepteur « deleted in colorectal cancer » (DCC).DCC est phosphorylé suite à la liaison de la nétrine-1 à son domaine extracellulaire. La phosphorylation de la tyrosine 1418 (Y1418) est notamment essentielle à la transduction de signaux en aval de nétrine-1 dans le système nerveux central des vertébrés. La caractérisation de deux nouvelles…
Advisors/Committee Members: Nathalie Lamarche (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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MLA ·
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Export
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APA (6th Edition):
Antoine-Bertrand, J. (2016). Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/h989r592r.pdf ; https://escholarship.mcgill.ca/concern/theses/b5644v38n
Chicago Manual of Style (16th Edition):
Antoine-Bertrand, Judith. “Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC.” 2016. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/h989r592r.pdf ; https://escholarship.mcgill.ca/concern/theses/b5644v38n.
MLA Handbook (7th Edition):
Antoine-Bertrand, Judith. “Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC.” 2016. Web. 16 Jan 2021.
Vancouver:
Antoine-Bertrand J. Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC. [Internet] [Doctoral dissertation]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/h989r592r.pdf ; https://escholarship.mcgill.ca/concern/theses/b5644v38n.
Council of Science Editors:
Antoine-Bertrand J. Signaling mechanisms underlying axon guidance downstream of the netrin-1 receptor DCC. [Doctoral Dissertation]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/h989r592r.pdf ; https://escholarship.mcgill.ca/concern/theses/b5644v38n
McGill University
15.
Kizilay, Ozge.
Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals.
Degree: PhD, Department of Anatomy and Cell Biology, 2018, McGill University
URL: https://escholarship.mcgill.ca/downloads/rj430710c.pdf
;
https://escholarship.mcgill.ca/concern/theses/k930c075g
► La cardiopathie ischémique / L'athérosclérose (ATH) est la principale cause de mortalité mondiale. Un nombre croissant de preuves indiquent que le vieillissement, ainsi que le…
(more)
▼ La cardiopathie ischémique / L'athérosclérose (ATH) est la principale cause de mortalité mondiale. Un nombre croissant de preuves indiquent que le vieillissement, ainsi que le léger état inflammatoire chronique qui lui est associé, contribuerait à la manifestation de l'ATH et à sa progression. Plus spécifiquement, l'activation immunitaire, par l'augmentation des cytokines pro-inflammatoires circulantes, joue un rôle central dans la déstabilisation de la plaque et sa rupture, donnant lieu à l'apparition
d'événements aigus coronariens (comme l'infarctus du myocarde). De plus, la présence de caractéristiques distinctives de sénescence dans les cellules de la plaque
d'athérome est une autre indication suggérant l'association de l'ATH avec un vieillissement biologique prématuré. Alors que les mécanismes impliqués dans la sénescence cellulaire ne sont pas parfaitement compris, les altérations de la fonction mitochondriale contribuent en grande partie à ce processus. Les mitochondries dysfonctionnelles ont en effet un rendement bioénergétique réduit, génèrent de hauts taux de dérivés réactifs de l'oxygène (DRO) et sont associées à une augmentation de la sécrétion de cytokines pro-inflammatoires. De ce fait, la preuve que le vieillissement vasculaire normal et l'ATH soient associés à la sénescence cellulaire et à un taux élevé de DRO entrainant un état inflammatoire chronique, fournit une logique pour les efforts thérapeutiques actuels dans la prévention de la progression de l'ATH à travers la modulation des cytokines. Les cellules souches mésenchymateuses multipotentes (CSMs) sont présentes dans presque tous les tissus et migrent vers les zones inflammatoires où elles modulent les réponses immunitaires. Ce constat sert de base à l'évaluation thérapeutique des CSMs dans diverses conditions, comme l'IM. Dans ce contexte, pour éviter le phénomène
d'immunogénicité, l'utilisation de CSMs autologues est préférable. La capacité des CSMs à modifier leur micro-environnement dépend principalement de leur activation et de la production inhérente
d'une variété de molécules solubles, connue sous le nom de 'sécrétome des CSMs'. Ce sécrétome présente généralement des propriétés anti-inflammatoires; néanmoins, les CSMs peuvent passer à un phénotype pro-inflammatoire via un processus encore mal compris, connu sous le nom de 'polarisation des CSMs'.Comme le déséquilibre de l'etat redox cellulaire est impliqué dans l'ATH, nous avons émis l'hypothèse suivante: le dysfonctionnement mitochondrial des CSMs provenant
d'individus atteint de l'ATH (CSMs-ATH) résulte en une augmentation des taux de DRO qui, en retour, induisent la polarisation de ces CSMs vers un phénotype pro-inflammatoire. De plus, nous avons proposé que la modulation de l'état redox des CSMs serait une stratégie utile pour l'amélioration de la fonction immunomodulaire des CSMs-ATH. Les contributions clé des travaux que j'ai conduits pour tester ces différentes hypothèses sont les suivantes: La dysfonction mitochondriale sous-tend la fonction immunomodulatrice altérée des ATH-MSC.…
Advisors/Committee Members: John Presley (Supervisor2), Inés Colmegna (Supervisor1).
Subjects/Keywords: Anatomy and Cell Biology
Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kizilay, O. (2018). Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/rj430710c.pdf ; https://escholarship.mcgill.ca/concern/theses/k930c075g
Chicago Manual of Style (16th Edition):
Kizilay, Ozge. “Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals.” 2018. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/rj430710c.pdf ; https://escholarship.mcgill.ca/concern/theses/k930c075g.
MLA Handbook (7th Edition):
Kizilay, Ozge. “Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals.” 2018. Web. 16 Jan 2021.
Vancouver:
Kizilay O. Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals. [Internet] [Doctoral dissertation]. McGill University; 2018. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/rj430710c.pdf ; https://escholarship.mcgill.ca/concern/theses/k930c075g.
Council of Science Editors:
Kizilay O. Mitochondrial dysfunction underlies the proinflammatory phenotype of multipotent mesenchymal stromal cells from atherosclerotic individuals. [Doctoral Dissertation]. McGill University; 2018. Available from: https://escholarship.mcgill.ca/downloads/rj430710c.pdf ; https://escholarship.mcgill.ca/concern/theses/k930c075g
McGill University
16.
Turgeon, Marc-Olivier.
Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome.
Degree: MS, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/0r967625k.pdf
;
https://escholarship.mcgill.ca/concern/theses/d791sj82q
► Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene cause central hypothyroidism. IGSF1 is a transmembrane glycoprotein of unknown function. It is expressed…
(more)
▼ Loss-of-function mutations in the X-linked immunoglobulin superfamily, member 1 (IGSF1) gene cause central hypothyroidism. IGSF1 is a transmembrane glycoprotein of unknown function. It is expressed in thyroid-stimulating hormone (TSH) producing thyrotrope cells of the anterior pituitary gland. The protein is co-translationally cleaved into N- and C-terminal domains (NTD and CTD). The CTD is trafficked to the plasma membrane, whereas the NTD is retained in the endoplasmic reticulum (ER). Most intragenic IGSF1 mutations in patients map to the CTD. To better understand IGSF1 function, we used the CRISPR-Cas9 system to introduce a loss-of-function mutation into the IGSF1-CTD in mice. The modified allele harbors a 312 bp deletion, removing part of exon 18 and intron 18. The resulting mRNA is expressed, though at greatly reduced levels relative to wild-type, and contains a novel hybrid exon. This exon introduces frame-shift and a premature stop codon, which affects the trafficking of the CTD. Igsf1 deficient mice show normal serum TSH levels and normal numbers of TSH-expressing thyrotropes. However, expression of the TSH subunits, Tshb and Cga, and TSH protein content are reduced in these animals relative to wild-type littermates. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates TSH synthesis and release. Importantly, pituitary TRH receptor (Trhr) mRNA levels are reduced in Igsf1 deficient males. When challenged with exogenous TRH, Igsf1 deficient mice release TSH, but to a significantly lesser extent than wild-type animals. The mice show similar impairments when endogenous TRH release is increased in response to reduced thyroid hormone feedback. Collectively, these results suggest that IGSF1 deficiency leads to central hypothyroidism via impairments in pituitary TRHR expression and/or downstream signaling.
Les mutations causant une perte de fonction du gène membre 1 de la superfamille des immunoglobulines (IGSF1) qui se trouve sur le chromosome X, sont responsables d'un syndrome d'hypothyroïdie centrale. IGSF1 est une glycoprotéine transmembranaire ayant une fonction inconnue. Elle est exprimée dans les thyréotropes de l'hypophyse produisant la thyréostimuline (TSH). IGSF1 est clivées au moment de la traduction et se sépare en deux domaines: le domaine du terminal N (NTD) et du terminal C (CTD). Le CTD est transporté à la surface cellulaire tandis que le NTD est retenu dans le réticulum endoplasmique (ER). La majorité des mutations intra-géniques de IGSF1, découverte chez les patients, se trouvent dans la région qui encode le CTD. Pour mieux comprendre le rôle de IGSF1, nous avons utilisé le système CRISPR-Cas9 pour introduire une mutation causant une perte de fonction de IGSF1-CTD. L'allèle modifié contient une perte de 312 paires de bases qui engendre la perte d'une partie de l'exon 18 et de l'intron 18. L'ARN résultant est exprimé, malgré un niveau d'expression très bas comparativement aux souris de type sauvage, et contient un nouvel exon hybride. Cet exon introduit une mutation qui affecte le cadre the…
Advisors/Committee Members: Daniel Bernard (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA (6th Edition):
Turgeon, M. (2016). Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/0r967625k.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj82q
Chicago Manual of Style (16th Edition):
Turgeon, Marc-Olivier. “Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome.” 2016. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/0r967625k.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj82q.
MLA Handbook (7th Edition):
Turgeon, Marc-Olivier. “Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome.” 2016. Web. 16 Jan 2021.
Vancouver:
Turgeon M. Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome. [Internet] [Masters thesis]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/0r967625k.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj82q.
Council of Science Editors:
Turgeon M. Impaired pituitary actions of thyrotropin-releasing hormone underlie central hypothyroidism in immunoglobulin superfamily, member 1 deficiency syndrome. [Masters Thesis]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/0r967625k.pdf ; https://escholarship.mcgill.ca/concern/theses/d791sj82q
McGill University
17.
Law, Fiona Yu Yin.
Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation.
Degree: PhD, Department of Anatomy and Cell Biology, 2017, McGill University
URL: https://escholarship.mcgill.ca/downloads/h702q880g.pdf
;
https://escholarship.mcgill.ca/concern/theses/x920g0226
► L'endocytose clathrine-dépendante (CME) est un processus cellulaire conservé qui résulte du bon fonctionnement de plusieurs protéines de transport. Parmi elles figure les GTPases de la…
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▼ L'endocytose clathrine-dépendante (CME) est un processus cellulaire conservé qui résulte du bon fonctionnement de plusieurs protéines de transport. Parmi elles figure les GTPases de la Rab5, qui jouent un rôle prépondérant pour coordonner le trafic vers les endosomes. Lors de la dégradation de cargos, Rab5 qui est présent au niveau des endosomes précoces (EE), est inhibée et retirée de la membrane, tandis que la GTPase Rab7, une protéine agissant au niveau des endosomes tardifs, est recrutée. Au cours de cette transition, Rab5 a besoin de la protéine d'activation des GTPases de la Rab5 (GAP) pour catalyser l'hydrolyse de sa GTP liée. Comment les GAPs de Rab5 se localisent de manière spécifique aux endosomes matures est un processus qu'il reste encore à élucider. Dans ce travail de recherche, j'utilise la protéine GAP de Rab5 du nématode Caenorhabditis elegans, TBC-2 et je démontre que la localisation de TBC-2 requiert que cette protéine aie sont domaine Pleckstrin Homology (PH) intact, ainsi que sa région englobant le domaine CC. Une perte du domaine PH de TBC-2 n'affecte pas l'activité GTPase de la protéine; en revanche, sans ce domaine, le patron de localisation est affecté et corrèle fortement avec un phénotype d'endosome tardifs. Une perte additionnelle du domaine CC abolit la capacité de ciblage de TBC-2. J'ai découvert que la capacité de liaison de ces deux domaines à leur cible est médiée par l'intermédiaire de la phosphoinositide 3-kinase (PI3K) de classe III, qui est générée pas PI3P. De manière cohérente et similaire à ce qu'on peut observer avec un mutant entrainant une perte de fonction (tbc-2), une perte de la sous-unité de PI3K induit un défaut au niveau du trafic cellulaire. Ces fait observés nous ont amené à emmètre comme hypothèse que TBC-2 utilise une stratégie basée sur la présence de PI3P pour permettre sa bonne localisation intracellulaire et que la liaison du domaine PH à PI3P est une étape importante pour la régulation de ce processus.De manière à identifier les protéines impliquées dans la localisation de TBC-2, un criblage génétique a été effectué et a permis d'isoler un régulateur potentiel de ce processus, vh45. Les nématodes ayant la mutation pour ce gène engendrent un phénotype endocytique similaire à tcbc-2 et la protéine est restreinte au côté basolateral. Ce gène est localisé sur le chromosome II, séparé du locus de tbc-2. Ce travail contribue à améliorer le niveau de connaissance relatif au(x) mécanisme(s) d'action employé par les GAPs de Rab5 pour la localiser de manière spatio-temporelle. Le contenu de ces recherches peut être appliqué de manière à mieux comprendre l'étiologie de certaines maladies qui découlent d'un défaut au niveau de la fonction des GAPs de la Rab5 et/ou du programme de maturation des endosomes.
Clathrin-mediated endocytosis (CME) is a conserved cellular process that requires the concerted functions of many trafficking proteins. Among those are the Rab GTPases, which coordinate endosome trafficking. In the degradation of cargo, the Rab5 GTPase present on the…
Advisors/Committee Members: Christian Rocheleau (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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CSE |
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Manager
APA (6th Edition):
Law, F. Y. Y. (2017). Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/h702q880g.pdf ; https://escholarship.mcgill.ca/concern/theses/x920g0226
Chicago Manual of Style (16th Edition):
Law, Fiona Yu Yin. “Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation.” 2017. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/h702q880g.pdf ; https://escholarship.mcgill.ca/concern/theses/x920g0226.
MLA Handbook (7th Edition):
Law, Fiona Yu Yin. “Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation.” 2017. Web. 16 Jan 2021.
Vancouver:
Law FYY. Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation. [Internet] [Doctoral dissertation]. McGill University; 2017. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/h702q880g.pdf ; https://escholarship.mcgill.ca/concern/theses/x920g0226.
Council of Science Editors:
Law FYY. Spatial regulation of TBC-2, a C. elegans Rab5 GAP, during endosome maturation. [Doctoral Dissertation]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/h702q880g.pdf ; https://escholarship.mcgill.ca/concern/theses/x920g0226
McGill University
18.
Lee, EunJoo.
From golgi to lipid droplet— understanding of organelle homeostasis.
Degree: PhD, Department of Anatomy and Cell Biology, 2017, McGill University
URL: https://escholarship.mcgill.ca/downloads/1831cn413.pdf
;
https://escholarship.mcgill.ca/concern/theses/jq085n82c
► Les organelles dans les cellules eucaryotes sont des compartiments membranaires qui assurent le contrôle localisé des activités cellulaires spécifiques. Les organelles sont essentielles pour l'organisation…
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▼ Les organelles dans les cellules eucaryotes sont des compartiments membranaires qui assurent le contrôle localisé des activités cellulaires spécifiques. Les organelles sont essentielles pour l'organisation et la fonction des cellules eucaryotes. Il est donc important de comprendre l'homéostasie des organelles : comment sont-elles créées et entretenues dans des conditions stables. Chaque organelle diffère dans sa fonction cellulaire et son homéostasie. L'appareil de Golgi est une organelle d'auto-organisation qui conserve son intégrité face à l'énorme afflux de lipides et de protéines. Grand nombre de protéines et de processus ont été cernés afin de maintenir les structures hautement dynamiques et l'équilibre de l'appareil de Golgi. Toutefois, le mécanisme par lequel les protéines biosynthétiques et les enzymes qi résident dans l'appareil de Golgi et qi le traversent est débattu depuis de nombreuses décennies. Afin d'élucider la manière dont les protéines et enzymes sont transportées à travers l'appareil de Golgi, nous avons conçu et entièrement caractérisé une nouvelle sonde fondée sur les anticorps qui peut mettre en lumière des enzymes de Golgi endogène in vivo. 'les anticorps de fusion' construits de cette façon sont considérablement plus petites que les anticorps conventionnels, et ils peuvent être conçus pour mettre en évidence les événements cellulaires. En outre, l'anticorps de fusion purifié par l'affinité conserve sa spécificité d'antigène. Avec les anticorps de fusion et la microscopie corrélative, les traits dynamiques des enzymes résidentes dans le Golgi endogènes peuvent être surveillées, et les résultats de cette étude contribueront à trouver des mécanismes de la rétention et du recyclage des enzymes qui résident dans la voie sécrétoire précoce de l'appareils de Golgi.
Organelles within eukaryotic cells are membrane-bound compartments that ensure the localized control of specific cellular activities. Organelles are essential to the organization and function of eukaryotic cells; therefore, it is important to understand organelle homeostasis— how organelles are formed and maintained in steady-state conditions. Organelles are unique in that they differ in their cellular function and homeostasis.The Golgi apparatus is a self-organizing organelle that maintains its structural integrity in the face of an enormous flux of lipid and proteins. A large number of proteins and processes have been identified in order to maintain the Golgi's highly dynamic structural equilibrium. However, the mechanisms by which biosynthetic proteins and Golgi-resident enzymes traverse the Golgi have been debated for many decades. To elucidate how proteins and enzymes are transported through the Golgi, we have designed and fully characterized a novel antibody-based probe able to highlight endogenous Golgi enzymes in vivo. 'Fusion antibodies' constructed this way are significantly smaller than conventional antibodies, and they can be engineered to highlight cellular events. Furthermore, affinity purified fusion antibodies retain…
Advisors/Committee Members: Tommy Nilsson (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, E. (2017). From golgi to lipid droplet— understanding of organelle homeostasis. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/1831cn413.pdf ; https://escholarship.mcgill.ca/concern/theses/jq085n82c
Chicago Manual of Style (16th Edition):
Lee, EunJoo. “From golgi to lipid droplet— understanding of organelle homeostasis.” 2017. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/1831cn413.pdf ; https://escholarship.mcgill.ca/concern/theses/jq085n82c.
MLA Handbook (7th Edition):
Lee, EunJoo. “From golgi to lipid droplet— understanding of organelle homeostasis.” 2017. Web. 16 Jan 2021.
Vancouver:
Lee E. From golgi to lipid droplet— understanding of organelle homeostasis. [Internet] [Doctoral dissertation]. McGill University; 2017. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/1831cn413.pdf ; https://escholarship.mcgill.ca/concern/theses/jq085n82c.
Council of Science Editors:
Lee E. From golgi to lipid droplet— understanding of organelle homeostasis. [Doctoral Dissertation]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/1831cn413.pdf ; https://escholarship.mcgill.ca/concern/theses/jq085n82c
McGill University
19.
Ben Djoudi Ouadda, Ali.
Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer.
Degree: PhD, Department of Anatomy and Cell Biology, 2017, McGill University
URL: https://escholarship.mcgill.ca/downloads/bc386n039.pdf
;
https://escholarship.mcgill.ca/concern/theses/70795b314
► Abstract The small Rho GTPase proteins act as molecular switches that regulate diverse cellular processes linked mostly to the actin-cytoskeleton remodeling making them essential regulators…
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▼ Abstract The small Rho GTPase proteins act as molecular switches that regulate diverse cellular processes linked mostly to the actin-cytoskeleton remodeling making them essential regulators of cell adhesion, migration and invasion. Dysregulation of their activities can result in different abnormal phenotypes particularly, tumor progression and metastasis. Hence, regulators of Rho GTPases such as Rho guanine nucleotide exchange factors (RhoGEFs) and Rho GTPase-activating proteins (RhoGAPs), are critical for normal cellular responses and are targets for subversion during oncogenic transformation. CdGAP (Cdc42 GTPase-activating protein) is a member of a well-conserved subfamily of RhoGAP proteins and a negative regulator of the small Rho GTPases, Rac1 and Cdc42. Associated with a rare developmental disorder (AOS, Adams-Oliver Syndrome) and required for a normal angiogenesis, CdGAP plays important roles in the regulation of cell migration and proliferation during early development. In addition, recent findings characterize CdGAP as an essential synergistic component between TGFβ and HER2/Neu/ErbB-2 signaling pathways which play a positive role in cancer, particularly breast cancer. CdGAP is regulated by lipid binding, protein-protein interactions and phosphorylation, still these mechanisms are not well understood. In this work we first investigate the interaction between CdGAP and its negative regulator, the endocytic protein Intersectin. Using an in vitro approach, we identify a novel, atypical xKx(K/R) (SKSKK) motif in the basic rich (BR) region of CdGAP that directly interacts with the Intersectin-SH3D domain. Moreover, the well-conserved motif is required for the regulation of CdGAP activity following Intersectin binding. Next, we investigate CdGAP phosphorylation and identify two regulatory phospho-serines in the C-terminal (CT) tail, Ser-1093 and Ser-1163, that are phosphorylated by the AGC-kinase family member, RSK1. Finally, we show that 14-3-3 family members bind and regulate both the cellular localization and activity of CdGAP in a Ser-1093 and Ser-1163 phosphorylation-dependent manner. Overall, this work provides two novel CdGAP-regulatory mechanisms that can be applied in therapeutic approaches targeting this RhoGAP, particularly in breast cancers.
RésuméLes petites protéines G de la famille Rho sont des commutateurs moléculaires qui contrôlent divers procédés cellulaires associés notamment, à la régulation du cytosquelette et jouent par conséquent, un rôle clé dans la régulation de la motilité cellulaire. La dérégulation de leur activité peut entrainer des aberrations se manifestant en particulier, par une progression du cancer et des métastases. Ainsi, les protéines régulatrices comme les facteurs d'échange de nucléotide (RhoGEFs) et les protéines activatrices des Rho GTPases (RhoGAPs) sont essentielles pour une signalisation cellulaire normale et sont en général, affectées lors des transformations oncogéniques. CdGAP (Cdc42-GTPase activating protein) est un membre d'une sous-famille de protéines…
Advisors/Committee Members: Nathalie Lamarche (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ben Djoudi Ouadda, A. (2017). Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/bc386n039.pdf ; https://escholarship.mcgill.ca/concern/theses/70795b314
Chicago Manual of Style (16th Edition):
Ben Djoudi Ouadda, Ali. “Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer.” 2017. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/bc386n039.pdf ; https://escholarship.mcgill.ca/concern/theses/70795b314.
MLA Handbook (7th Edition):
Ben Djoudi Ouadda, Ali. “Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer.” 2017. Web. 16 Jan 2021.
Vancouver:
Ben Djoudi Ouadda A. Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer. [Internet] [Doctoral dissertation]. McGill University; 2017. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/bc386n039.pdf ; https://escholarship.mcgill.ca/concern/theses/70795b314.
Council of Science Editors:
Ben Djoudi Ouadda A. Identification of novel regulatory mechanisms for for Cdc42 GTPase-activating protein CdGAP/ARHGAP31, a protein involved in development and cancer. [Doctoral Dissertation]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/bc386n039.pdf ; https://escholarship.mcgill.ca/concern/theses/70795b314
McGill University
20.
Skorobogata, Olga.
Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors.
Degree: PhD, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/ms35tb91v.pdf
;
https://escholarship.mcgill.ca/concern/theses/hh63sz57g
► A highly conserved Epidermal Growth Factor Receptor (EGFR) signaling pathway specifies vulval cell fate induction during C. elegans development. LET-23 EGFR has to be present…
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▼ A highly conserved Epidermal Growth Factor Receptor (EGFR) signaling pathway specifies vulval
cell fate induction during C. elegans development. LET-23 EGFR has to be present on the basolateral membrane of the polarized vulval precursor cells (VPCs) in order to engage and transmit EGF signal. In mammals, EGFR also localizes to basolateral membranes of epithelial cells. Excessive activation of the EGFR signaling pathway has been implicated in cancer and a majority of cancers originate from epithelial cells. Thus, C. elegans VPCs provide a unique in vivo model to study EGFR signaling and localization in polarized epithelium. We conducted a genetic screen for essential regulators of EGFR signalling and identified mutations in the agef-1 and dhc-1, which code for an Arf GTPase guanine nucleotide exchange factor and the heavy chain of the dynein minus-end microtubule motor protein, respectively.A partial loss-of-function mutation in agef-1 enhances EGFR signaling in sensitized backgrounds as well as leads to secretory defects in multiple tissues. Additionally, agef-1 mutant animals have enlarged late endosomes/lysosomes in the coelomocytes. These phenotypes suggest that both secretory and endocytic trafficking pathways are affected in agef-1 mutants. We found that AGEF-1 functions with two Arf GTPases and the AP-1 clathrin adaptor complex to negatively regulate EGFR signaling by antagonizing the basolateral localization of the receptor. Taken together with the recently described role of the AP-1 adaptor in the maintenance of epithelial polarity, AGEF-1 might regulate LET-23 EGFR signaling via multiple mechanisms: directly by antagonizing basolateral localization of the receptor and indirectly by maintaining epithelial polarity in the VPCs. A human homolog of AGEF-1 is mutated in numerous cancer
cell lines supporting a tumor suppressive function in humans. Our recent data indicate that a small GTPase RAB-10 is required for multiple agef-1 phenotypes, including negatively regulating LET-23 EGFR signaling in the vulva and affecting the size of late endosomes. This effect is specific to RAB-10 and suggests that AGEF-1 and RAB-10 might function closely in an antagonistic manner.dhc-1(vh22) animals are small and temperature sensitive, with increased embryonic lethality due
cell division defects at a restrictive temperature of 20°C. Loss of dhc-1 results in increased LET-23 EGFR signaling in sensitized backgrounds suggesting that DHC-1 is a negative regulator of EGFR signaling. LET-23::GFP accumulates in plasma membrane proximal foci of the VPCs in dhc-1 mutants suggesting that dynein functions at an early step of EGFR endosomal trafficking. Moreover, a late endosomal GTPase RAB-7 also antagonises LET-23 EGFR signaling and its loss leads to LET-23::GFP accumulation in cytoplasmic foci. Given the ability of mammalian Rab7 to engage dynein to promote late endosome trafficking towards the lysosome, it is possible that RAB-7 and DHC-1 might function together at a later step of EGFR trafficking for degradation. Our recent findings…
Advisors/Committee Members: Christian Rocheleau (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Skorobogata, O. (2016). Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/ms35tb91v.pdf ; https://escholarship.mcgill.ca/concern/theses/hh63sz57g
Chicago Manual of Style (16th Edition):
Skorobogata, Olga. “Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors.” 2016. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/ms35tb91v.pdf ; https://escholarship.mcgill.ca/concern/theses/hh63sz57g.
MLA Handbook (7th Edition):
Skorobogata, Olga. “Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors.” 2016. Web. 16 Jan 2021.
Vancouver:
Skorobogata O. Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors. [Internet] [Doctoral dissertation]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/ms35tb91v.pdf ; https://escholarship.mcgill.ca/concern/theses/hh63sz57g.
Council of Science Editors:
Skorobogata O. Regulation of «C. elegans» epidermal growth factor receptor signaling and trafficking by rabs, arfs and motors. [Doctoral Dissertation]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/ms35tb91v.pdf ; https://escholarship.mcgill.ca/concern/theses/hh63sz57g
McGill University
21.
Lynham, Jeffrey.
Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease.
Degree: MS, Department of Anatomy and Cell Biology, 2017, McGill University
URL: https://escholarship.mcgill.ca/downloads/kh04ds24k.pdf
;
https://escholarship.mcgill.ca/concern/theses/qb98mj07s
► Des études réalisées à partir de modèles murins transgéniques et de tissus humains post-mortem ont montré que l'activité de la caspase-6 est impliquée dans les…
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▼ Des études réalisées à partir de modèles murins transgéniques et de tissus humains post-mortem ont montré que l'activité de la caspase-6 est impliquée dans les troubles cognitifs liés à l'âge et la maladie d'Alzheimer, suggérant que la caspase-6 pourrait être une cible thérapeutique potentielle pour ces pathologies. Bien que plusieurs inhibiteurs de caspase-6 aient été identifiés, la plupart d'entre eux ne sont pas sélectifs. Dans cette étude, en utilisant une nouvelle approche génétique, nous avons identifié une poche allostérique non conservée pouvant lier des petites molécules. Un criblage in silico de 77 000 molécules contre cette poche allostérique a permis d'identifier 54 inhibiteurs potentiels de caspase-6. Ce travail de thèse se concentre sur 15 de ces composés, appartenant à banque de composés Sigma-Aldrich. Des analyses in vitro ont identifié le composé 10 et ses analogues comme étant les inhibiteurs de caspase-6 les plus puissants et sélectifs. Des analyses cinétiques ont montré que ces composés inhibent la caspase-6 de manière non-compétitive. De plus, ces composés sont non toxiques et diminuent l'activité de la caspase-6 dans les cellules HCT116, mais sont cytotoxiques dans les cellules HEK293T. Enfin, nos études ont révélé que le composé 10P serait la molécule qui pourrait potentiellement servir de base pour l'optimisation de composés allostériques plus puissants, sélectifs et non toxiques. En conclusion, en plus d'avoir identifié de nouveaux inhibiteurs de caspase-6, nous avons validé une nouvelle approche pour la découverte d'inhibiteurs allostériques.
Knock-in transgenic mouse models and human post-mortem studies have demonstrated Caspase-6 (Casp6) activity to be involved in both age-dependent cognitive impairment and Alzheimer disease, suggesting Casp6 as a potential therapeutic target. Although Casp6 inhibitors have been identified, many of them are non-selective. Here, we show that by using a novel human genetic approach, we identified a non-conserved allosteric pocket that bears favorable tertiary architecture for accommodating small molecules. An in silico screen of 77,000 diverse molecules against this pocket identified fifty-four potential Casp6 inhibitors. This thesis will focus on the fifteen hits identified from the Sigma-Aldrich commercial library. In vitro screening of these compounds identified compound 10 and its analogues as the most potent and selective Casp6 inhibitors. In addition, kinetic analyses show that these compounds inhibit Casp6 through a non-competitive mode of inhibition. Furthermore, these compounds are non-toxic and reduce Casp6 activity in HCT116 cells, whereas they induce cytotoxicity in HEK293T cells. Finally, extensive compound 10 analogue screens have identified compound 10P as our hit compound that could potentially be used as a starting point for medicinal chemistry for the optimization of a more potent, selective and non-toxic allosteric inhibitor. Together, not only do these findings identify a novel class of Casp6 inhibitors, but also validate a novel…
Advisors/Committee Members: Andrea LeBlanc (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA (6th Edition):
Lynham, J. (2017). Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/kh04ds24k.pdf ; https://escholarship.mcgill.ca/concern/theses/qb98mj07s
Chicago Manual of Style (16th Edition):
Lynham, Jeffrey. “Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease.” 2017. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/kh04ds24k.pdf ; https://escholarship.mcgill.ca/concern/theses/qb98mj07s.
MLA Handbook (7th Edition):
Lynham, Jeffrey. “Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease.” 2017. Web. 16 Jan 2021.
Vancouver:
Lynham J. Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease. [Internet] [Masters thesis]. McGill University; 2017. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/kh04ds24k.pdf ; https://escholarship.mcgill.ca/concern/theses/qb98mj07s.
Council of Science Editors:
Lynham J. Identification of allosteric inhibitors against caspase-6 activity in Alzheimer's disease. [Masters Thesis]. McGill University; 2017. Available from: https://escholarship.mcgill.ca/downloads/kh04ds24k.pdf ; https://escholarship.mcgill.ca/concern/theses/qb98mj07s
McGill University
22.
Fabre, Lucien.
Study of bacterial transport membrane proteins by single particle electron microscopy.
Degree: PhD, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/9g54xm34j.pdf
;
https://escholarship.mcgill.ca/concern/theses/w6634632j
► La croissance et la survie des bactéries sont directement liées à leurs capacités à se nourrir et à se défendre. Cela implique une interaction efficace…
(more)
▼ La croissance et la survie des bactéries sont directement liées à leurs capacités à se nourrir et à se défendre. Cela implique une interaction efficace entre l'organisme et l'environnement. Leur enveloppe complexe est la clé de cette interaction intime qui a permis aux bactéries de s'adapter avec succès à une variété de niches écologiques. L'objectif de ma thèse était
d'étudier les mécanismes de transport des protéines membranaires par microscopie électronique et particules isolées (SP-EM). Pour cela, j'ai choisi
d'étudier un transporteur ATP-dépendant (MalFGK2), un prototype AB-toxines (Anthrax) et un transporteur impliqué dans la multi-résistance médicamenteuse (TriABC). 1) Le transporteur du maltose MalFGK2, un prototype de transporteur (ABC) ATP-dépendantMalFGK2 est un importateur de maltose
d'E. Coli. Au cours du transport, le domaine membranaire de MalFG s'ouvre soit vers l'intérieur de la cellule soit vers son extérieur en réponse la fixation de l'ATP et à son hydrolyse. Le transport nécessite une protéine périplasmique MalE. Dans la littérature, les rôles distincts du nucléotide, MalE et du maltose dans le cycle de la catalyse n'étaient pas clairs. Nos résultats en SP-EM présentent les premières structures de MalFGK2 lié à divers nucléotides en l'absence de MalE ainsi que la première structure de MalFGK2-MalE en l'absence de nucléotides et de maltose. Nous avons démontré que l'ATP et MalE jouent un rôle essentiel, distinct et complémentaire, pour alimenter le cycle du transport du maltose. Il indique également que le maltose influence sur la conformation du transporteur. 2) Les toxines de l'anthrax, le meilleur prototype caractérisé de la famille des AB-toxines (ou toxines binaires) Les toxines AB de Bacillus anthracis sont composées de l'antigène protecteur (PA) et deux protéines: le facteur de l'œdème (EF) et le facteur létal (LF). PA s'organise en un heptamère ou octamère qui se transforme en un pore permettant à EF et LF
d'entrer dans la cellule. Nos résultats nous permettent de proposer un modèle selon lequel l'arrangement moléculaire des 3 LFs et leurs interactions les uns avec les autres, ainsi que le décalage de symétrie entre les 3 molécules de LF et le complexe PA heptamérique, définit l'ordre de translocation et jouent un rôle important pour maintenir l'efficacité de la translocation indépendamment de la concentration de LF. 3) La pompe à efflux du triclosan TriABC, un modèle de transporteur causant une multi-résistance médicamenteuseTriABC est un complexe exprimé par Pseudomonas aeruginosa lui permettant
d'expulser le triclosan et le SDS. Il comprend une pompe (TriC) et deux protéines de fusion de la membrane : TriA et TriB. Notre analyse
d'images nous a permis de distinguer TriA, TriB et TriC dans le complexe assemblé. Cela était inconnu jusqu'à lors. De plus, nos résultats préliminaires par microscopie électronique à froid (cryo-EM) nous permettent de distinguer les différents domaines de TriC incluant la poche
d'entrée du SDS/triclosan. Approfondir l'analyse
d'image devrait permettre de…
Advisors/Committee Members: Isabelle Rouiller (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Fabre, L. (2016). Study of bacterial transport membrane proteins by single particle electron microscopy. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/9g54xm34j.pdf ; https://escholarship.mcgill.ca/concern/theses/w6634632j
Chicago Manual of Style (16th Edition):
Fabre, Lucien. “Study of bacterial transport membrane proteins by single particle electron microscopy.” 2016. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/9g54xm34j.pdf ; https://escholarship.mcgill.ca/concern/theses/w6634632j.
MLA Handbook (7th Edition):
Fabre, Lucien. “Study of bacterial transport membrane proteins by single particle electron microscopy.” 2016. Web. 16 Jan 2021.
Vancouver:
Fabre L. Study of bacterial transport membrane proteins by single particle electron microscopy. [Internet] [Doctoral dissertation]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/9g54xm34j.pdf ; https://escholarship.mcgill.ca/concern/theses/w6634632j.
Council of Science Editors:
Fabre L. Study of bacterial transport membrane proteins by single particle electron microscopy. [Doctoral Dissertation]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/9g54xm34j.pdf ; https://escholarship.mcgill.ca/concern/theses/w6634632j
McGill University
23.
Wang, Jae Woong.
Murine hypoglossal motor neuron topographic map development.
Degree: MS, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/n009w5037.pdf
;
https://escholarship.mcgill.ca/concern/theses/8336h4443
► Les motoneurones (MNs) sont des cellules neuronales essentielles qui jouent des rôles uniques dans les circuits moteurs fonctionnels. Au cours du développement, les MNs somatiques…
(more)
▼ Les motoneurones (MNs) sont des cellules neuronales essentielles qui jouent des rôles uniques dans les circuits moteurs fonctionnels. Au cours du développement, les MNs somatiques s'organisent topographiquement en sous-types distincts lesquels innervent des cibles musculaires spécifiques. L'acquisition de groupements de MN topologiquement définis est un processus essentiel au cours du développement du noyau hypoglosse de la souris, une structure située dans le tronc cérébral caudal. Les MNs hypoglossaux innervent les muscles de la langue, contrôlant ainsi des fonctions vitales telles que la mastication, la déglutition et la respiration. Ces MNs suscitent un intérêt considérable en recherche en raison de leur vulnérabilité à la dégénérescence dans des maladies neurodégénératives comme la Sclérose Latérale Amyotrophique (SLA), où la perte de MNs hypoglossaux est un facteur contribuant à la morbidité et la mortalité des patients en altérant l'alimentation et les fonctions respiratoires. La mise en place de cartes précises de MN dans le noyau hypoglosse est essentielle pour la formation de circuits moteurs fonctionnels commandés par ces MNs hypoglossaux qui innervent les muscles de la langue. Cependant, on sait peu sur les mécanismes sous-jacents de la création des cartes somatotopiques de MN hypoglossaux. Pour remédier à ce manque d'information, le travail présenté dans cette thèse a cherché à comprendre les mécanismes moléculaires contrôlant la mise en place des identités et des topologies spécifiques des MN hypoglossaux en utilisant une combinaison d'études d'expression in vivo et d'analyse par perturbation génétique. Ces recherches ont fourni la démonstration que l'expression de trois facteurs de transcription; appelés Runx1, FOXP1 et SCIP; définit les subdivisions anatomiques du noyau hypoglosse, lesquelles subdivisions possèdent des MNs avec des phénotypes uniques topologiques, de neurotransmission, et de pouvoir tampon du calcium. Plus précisément, Runx1 et SCIP sont exprimés dans un groupe de MNs hypoglossaux ventro-médians qui innervent les muscles impliqués dans protrusion de la langue. En revanche, FOXP1 est exprimé dans un groupe distinct de MNs hypoglossaux, groupe situé en position dorsale par rapport aux MNs exprimant Runx1, et ce groupe de MNs exprimant FOXP1 contrôleraient la rétraction de la langue. En outre, les résultats d'études de gain de fonction in vivo fournissent des preuves que Runx1 est important pour l'établissement de la topologie des MNs dans le noyau hypoglosse, au moins en partie, en limitant l'expression de FOXP1 et SCIP. Ces résultats combinés suggèrent que la mosaïque d'expression bien circonscrite de facteurs de transcription tels que Runx1, FOXP1 et SCIP contribue au développement des circuits moteurs vitaux qui contrôlent la protrusion et la rétraction de la langue, en partie grâce à la mise en place de la carte topographique de l'hypoglosse.
Motor neurons (MNs) are essential neuronal cells that play unique roles in functional motor circuits. During development, somatic MNs…
Advisors/Committee Members: Stefano Stifani (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, J. W. (2016). Murine hypoglossal motor neuron topographic map development. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/n009w5037.pdf ; https://escholarship.mcgill.ca/concern/theses/8336h4443
Chicago Manual of Style (16th Edition):
Wang, Jae Woong. “Murine hypoglossal motor neuron topographic map development.” 2016. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/n009w5037.pdf ; https://escholarship.mcgill.ca/concern/theses/8336h4443.
MLA Handbook (7th Edition):
Wang, Jae Woong. “Murine hypoglossal motor neuron topographic map development.” 2016. Web. 16 Jan 2021.
Vancouver:
Wang JW. Murine hypoglossal motor neuron topographic map development. [Internet] [Masters thesis]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/n009w5037.pdf ; https://escholarship.mcgill.ca/concern/theses/8336h4443.
Council of Science Editors:
Wang JW. Murine hypoglossal motor neuron topographic map development. [Masters Thesis]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/n009w5037.pdf ; https://escholarship.mcgill.ca/concern/theses/8336h4443
McGill University
24.
Heidari, Maryam.
Semaphorin-3A, a regulator of immune system.
Degree: PhD, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/w37639639.pdf
;
https://escholarship.mcgill.ca/concern/theses/8623j1628
► Background: Atherosclerosis a global health issue and first leading of myocardial infarction and strokes is an immunity-related disease. Recent data indicate that neural guidance molecules…
(more)
▼ Background: Atherosclerosis a global health issue and first leading of myocardial infarction and strokes is an immunity-related disease. Recent data indicate that neural guidance molecules including Semaphorin-3A have immune regulation function. It has been shown that in some inflammatory diseases such as rheumatoid arthritis, the serum levels of Sema-3A is lower in patients [18, 112] and administration of Sema-3A in animal models of these diseases showed a protective effect in the progress of diseases [18]. Both Sema-3A and its receptors are expressed by most of immune cells involved in atherosclerosis such as monocytes, macrophages, and T cells and regulates the function of these cells [61, 125, 91], however, the effect of Sema-3A on atherosclerotic plaque progression is not known. We hypothesize that Sema-3A may have atheroprotective effect by regulating macrophage function and inflammation resolution. Methods: In vivo: ApoE-/- mice were electroporated with Sema-3A or control plasmid to overexpress the protein (plasma Sema-3A increased levels were verified by ELISA), and kept on high fat diet for 9 and 13 weeks. Plaque size was determined with oil red O staining in aortic sinus, BCA, and aorta. Plaque characterization was performed by immunostaing. To investigate the effect of Sema-3A on acute inflammation C57bl6 mice were treated with Sema-3A or control plasmids. Five days later LPS or VEH were injected into the skin of the ears. LPS-induced-inflammation was studied 48 hours later.In vitro: Bone-marrow-derived monocytes were obtained from C57bl6 mice and differentiated into macrophages by M-CSF. Macrophages were polarized to M1 or M2 types using IFN-gamma or IL-4 respectively. Western blotting was performed to determine the expression of Sema-3A receptors on macrophages. M1 and M2 macrophage migration was assessed by boyden chambers assay. mRNA levels of integrins was performed by q-PCR and activation of some integrins were measured on human PBMCs derived from healthy donors, by flow cytometry. Results: Our findings show that atherosclerotic plaque is significantly smaller in Sema-3A overexpressing as compared to control mice in BCA, aortic sinus, and aorta. The plaque stability was comparable in both groups, however, plaque macrophage content was twice lower in Sema-3A overexpressing mice. This was associated with less circulating monocytes in this group. Moreover, we found that even though the monocyte recruitment to the plaque was not influenced by Sema-3A, M2 macrophage In vitro migration was increased by Sema-3A, which could explain lower macrophage content in the plaques of these mice. Further analysis showed that increased M2 macrophage migration by sema-3A was associated with higher activation of β1-integrins and phosphorylation of focal adhesion kinase in these cells. The negative immuno-regulatory effect of Sema-3A was also confirmed by decreased LPS-induced acute inflammation by Sema-3A. LPS-induced ear thickening was significantly decreased in Sema-3A overexpressing as compared to control mice. Our…
Advisors/Committee Members: Craig A. Mandato (Supervisor2), Stephanie Lehoux (Supervisor1).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
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Export
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APA (6th Edition):
Heidari, M. (2016). Semaphorin-3A, a regulator of immune system. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/w37639639.pdf ; https://escholarship.mcgill.ca/concern/theses/8623j1628
Chicago Manual of Style (16th Edition):
Heidari, Maryam. “Semaphorin-3A, a regulator of immune system.” 2016. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/w37639639.pdf ; https://escholarship.mcgill.ca/concern/theses/8623j1628.
MLA Handbook (7th Edition):
Heidari, Maryam. “Semaphorin-3A, a regulator of immune system.” 2016. Web. 16 Jan 2021.
Vancouver:
Heidari M. Semaphorin-3A, a regulator of immune system. [Internet] [Doctoral dissertation]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/w37639639.pdf ; https://escholarship.mcgill.ca/concern/theses/8623j1628.
Council of Science Editors:
Heidari M. Semaphorin-3A, a regulator of immune system. [Doctoral Dissertation]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/w37639639.pdf ; https://escholarship.mcgill.ca/concern/theses/8623j1628
McGill University
25.
Chin, Preston.
EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification.
Degree: MS, Department of Anatomy and Cell Biology, 2016, McGill University
URL: https://escholarship.mcgill.ca/downloads/vd66w256w.pdf
;
https://escholarship.mcgill.ca/concern/theses/qz20sw60n
► La Ras/Protèine Kinase Activée par des Mitogènes (MAPK) voie de signalisation régule beaucoup d'événements de développement, y compris la détermination du sort de la cellule…
(more)
▼ La Ras/Protèine Kinase Activée par des Mitogènes (MAPK) voie de signalisation régule beaucoup
d'événements de développement, y compris la détermination du sort de la cellule de canal excréteur (EDC) et de son entretien. Un manque
d'une EDC provoque une létalité de tige phénotypiquement distincte en raison
d'une incapacité à excréter les déchets liquides. Le protéines
d'échafaudage kinase suppresseur de Ras (KSR), KSR-1 et KSR-2, sont redondante nécessaire pour Ras/MAPK signalisation et la spécification de la EDC. ksr-1(2526) mutants nuls présentent un phénotype de type sauvage, mais ils sont sensibles à des mutations qui réduisent la signalisation Ras/MAPK. Par la suite, un écran génétique identifiée vh20 comme un allèle candidat pour Y39G10AR.7, que j'ai appelé depuis ekl-7 comme un activateur de ksr-1 létalité (ekl). Les ekl-7(vh20); ksr-1(2526) doubles mutants ont une fréquence de létalité de tige de 35%. Le vh20 E422K mutation faux-sens perturbe un domaine chargé négativement C-terminale. EKL-7 est une protéine spécifique à Caenorhabditis. Mais, les alignements de protéines ont identifié un groupe de consensus sites de phosphorylation ERK (PX-S/T-P et S/T-P) et les sites
d'accueil ERK (FXFP et
D domaine) similaire à ceux trouvés dans LIN-1 et EOR-1, les substrats en aval de MPK-1 ERK. Je hypothèse que EKL-7 est un nouveau substrat en aval de MPK-1 ERK qui régule positivement le sort EDC ou son entretien. Pour caractériser la létalité de tige des mutants de ekl-7(vh20); ksr-1(n2526), j'ai généré des animaux portant une marque de la EDC et jonction apicale. Alors que les mutants ekl-7(vh20) sont essentiellement de type sauvage, les mutants ekl-7(vh20); ksr-1(n2526) ont les EDCs qui ne autofuse correctement dans une cellule toroïdal sans soudure en raison
d'une panne
d'exprimer aff-1, une protéine fusogène nécessaire pour autofusion. Ceci suggère que EKL-7 pourrait avoir un rôle spécifique dans EDC autofusion lors de sa spécification. Pour élucider la façon common ekl-7(vh20) fonctions au sein de la voie de signalisation Ras/MAPK, j'ai produit des doubles mutants avec lin-1 ou eor-1 parce que ces régulateurs de transcription fonctionnent en aval de MPK-1 ERK et ont démontré des effets synergiques lors de la spécification du sort EDC. J'ai observé que les deux mutants, ekl-7(vh20); lin-1(n2515) et ekl-7(vh20); eor-1(cs28) démontrent améliorée létalité en forme de tige, ce qui suggère que EKL-7 fonctionne en parallèle à LIN-1 et EOR-1. En plus, ekl-7(vh20); lin-1(n2515) et ekl-7(vh20); eor-1(cs28) mutants montrent divers défauts dans leurs systèmes excréteurs. La capacité de la voie Ras/MAPK pour réguler de nombreux processus de développement dépend probablement à la suite de substrats en aval de MPK-1 ERK qui sont disponibles dans un type de cellule spécifique. EKL-7 pourrait être une spécificité de facteur important qui fonctionne en coordination avec LIN-1 et EOR-1 pour réguler positivement le sort EDC et de son entretien, par opposition à la promotion
d'autres processus cellulaires régulés par de…
Advisors/Committee Members: Christian Rocheleau (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chin, P. (2016). EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/vd66w256w.pdf ; https://escholarship.mcgill.ca/concern/theses/qz20sw60n
Chicago Manual of Style (16th Edition):
Chin, Preston. “EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification.” 2016. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/vd66w256w.pdf ; https://escholarship.mcgill.ca/concern/theses/qz20sw60n.
MLA Handbook (7th Edition):
Chin, Preston. “EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification.” 2016. Web. 16 Jan 2021.
Vancouver:
Chin P. EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification. [Internet] [Masters thesis]. McGill University; 2016. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/vd66w256w.pdf ; https://escholarship.mcgill.ca/concern/theses/qz20sw60n.
Council of Science Editors:
Chin P. EKL-7 is a putative MPK-1 ERK target during C. «elegans» excretory duct cell fate specification. [Masters Thesis]. McGill University; 2016. Available from: https://escholarship.mcgill.ca/downloads/vd66w256w.pdf ; https://escholarship.mcgill.ca/concern/theses/qz20sw60n
McGill University
26.
Yang, Shun Kai.
Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation.
Degree: MS, Department of Anatomy and Cell Biology, 2015, McGill University
URL: https://escholarship.mcgill.ca/downloads/ff365807x.pdf
;
https://escholarship.mcgill.ca/concern/theses/8049g786c
► Eukaryotic actins are involved in many important processes in the cell, but how they evolved from prokaryotic actins remains unclear. Previous research shows that one…
(more)
▼ Eukaryotic actins are involved in many important processes in the cell, but how they evolved from prokaryotic actins remains unclear. Previous research shows that one of these bacterial actins, actin-like-filament-A (AlfA) shares many characteristics with eukaryotic actin. AlfA is capable of forming filamentous structures, which segregate plasmids in Bacillus subtilis natto during cell division. Research on AlfA may help to explicate the evolutionary link between these two actin families. To accomplish this objective, a high-resolution structure of the AlfA filament by X-ray crystallography would provide a better understanding of AlfA structure. Additionally, biochemical studies and functional assays will elucidate the function and dynamics of AlfA.Initially, we optimized the purification of AlfA using a novel expression approach to generate purified protein in quantities sufficient for structural characterization. AlfA mutants were generated to help define the polymerization interfaces, and our biochemical studies and EM micrographs showed that R78D/K79D mutants are polymerization incompetent. We have begun crystallizing AlfA and mutants for X-ray analysis, and one of the crystal hits was optimized using additive screen to produce hexagonal crystals. Our functional assays in vivo revealed that the truncation of AlfA resulted in plasmid DNA loss. Our results suggest that AlfA polymerization is required for ensuring plasmid inheritance.Our long-term goal is to generate an accurate model of the filament by docking a high- resolution crystal structure into a medium resolution cryo-EM structure. This may enhance our understanding of how eukaryotic actins were evolved, and aid developing new pharmaceuticals to target the segregation of virulence plasmids in multidrug- resistant bacteria.
Les actines eucaryotiques sont impliqués dans de nombreux processus cellulaires. Même si elles ont été extensivement étudiées, peu est compris quant à leur évolution à partir des actines procaryotiques. Actin-like filament A (AlfA) est une actine bactérienne comprenant des caractéristiques semblables aux actines eucaryotiques. AlfA forme des structures filamenteuses pour ségréguer les plasmides de Bacillus subtilis natto lors de sa fission cellulaire. L’étude d’AlfA pourrait élucider le lien évolutionnaire entre les actines eucaryotiques et procaryotiques. Or, une structure à haute résolution obtenue par cristallographie aux rayons X, ainsi que des études biochimiques et structurelles permettront de mieux comprendre la structure et la fonction d’AlfA.Nous avons optimisé la purification d’AlfA en utilisant une nouvelle méthode d’expression avec un rendement suffisant pour la caractérisation structurale. Des mutations dans AlfA ont aidé à établir les interfaces de polymérisation. À l’aide d’études biochimiques et de visualisions de micrographes par microscope électronique, nous avons déterminé que les mutations à R78D/K79D empêchent la polymérisation d’AlfA. Nos tentatives de cristallisation d’AlfA et…
Advisors/Committee Members: Craig A. Mandato (Internal/Cosupervisor2), Justin Kollman (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA (6th Edition):
Yang, S. K. (2015). Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/ff365807x.pdf ; https://escholarship.mcgill.ca/concern/theses/8049g786c
Chicago Manual of Style (16th Edition):
Yang, Shun Kai. “Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation.” 2015. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/ff365807x.pdf ; https://escholarship.mcgill.ca/concern/theses/8049g786c.
MLA Handbook (7th Edition):
Yang, Shun Kai. “Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation.” 2015. Web. 16 Jan 2021.
Vancouver:
Yang SK. Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation. [Internet] [Masters thesis]. McGill University; 2015. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/ff365807x.pdf ; https://escholarship.mcgill.ca/concern/theses/8049g786c.
Council of Science Editors:
Yang SK. Purification and initial structural characterization of AlfA a novel bacterial actin necessary for plasmid segregation. [Masters Thesis]. McGill University; 2015. Available from: https://escholarship.mcgill.ca/downloads/ff365807x.pdf ; https://escholarship.mcgill.ca/concern/theses/8049g786c
McGill University
27.
Lee, Chae Syng.
N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly.
Degree: MS, Department of Anatomy and Cell Biology, 2015, McGill University
URL: https://escholarship.mcgill.ca/downloads/jq085p135.pdf
;
https://escholarship.mcgill.ca/concern/theses/fb494c25m
► La famille des fibulines comprend huit glycoprotéines extracellulaires, caractérisées par un nombre variable de domaines de type «calcium-binding epidermal growth factor» (cbEGF), suivis de modules…
(more)
▼ La famille des fibulines comprend huit glycoprotéines extracellulaires, caractérisées par un nombre variable de domaines de type «calcium-binding epidermal growth factor» (cbEGF), suivis de modules de type fibuline en C-terminal. Les fibulines-3, -4 et -5 consistent en six domaines cbEGF suivis par le domaine C-terminal. Ces fibulines sont exprimées dans divers tissus élastiques, incluant les vaisseaux sanguins, les poumons et la peau, et jouent un rôle important dans l’élastogénèse. Notamment, des mutations dans la fibuline-4 sont responsables de maladies cardiovasculaires et cutanées, et son absence dans les modèles de souris cause une mort prénatale. La fibuline-4 humaine contient deux groupes glycanes de fonction inconnue, un situé dans le cbEGF à la position Asn198, et le second dans le domaine C-terminal à la position Asn394. La fibuline-4 recombinante comportant un tag histidine a été exprimée dans des cellules HEK293H, puis purifiée par chromatographie d’affinité. L’affinité de la fibuline-4 pour la tropoelastine après déglycosylation enzymatique étant augmentée, nous avons supposé que la glycosylation de la fibuline-4 joue un rôle essentiel dans la formation des fibres élastiques. Pour tester cette hypothèse, nous avons généré des mutants de la fibuline-4 dépourvue d’un ou des deux sites de N-glycosylation. Les constructions encodant les mutants ont été transfectées dans des cellules HEK293H pour s`assurer que les modifications post-traductionnelles étaient adéquates. Tous les mutants étaient sécrétés en quantité significativement inférieure à la protéine normale, et montraient une activation de la réponse aux protéines malformées, indiquant que le processus repliement conformationnel de conformation de la protéine au sein du réticulum endoplasmique était bloqué. Ce résultat démontre que la N-glycosylation de la fibuline-4 est important pour assurer la sécrétion de la protéine dans la matrice extracellulaire. Afin d’identifier un bon modèle de culture cellulaire pour l’étude de l’élastogénèse, l’expression de protéines élastogéniques a été analysée par immunofluorescence dans plusieurs lignées cellulaires. Les cellules musculaires lisses aortiques de rats (PAC1) ont été sélectionnées et transfectées avec la fibuline-4 de type sauvage ou mutante afin d’étudier l’impact de la glycosylation sur la formation des fibres élastiques. Nous avons découvert que la surexpression de la fibuline-4 augmente la sécrétion de tropoélastine, et que les mutants induisent un meilleur assemblage de la tropoélastine dans les fibres extracellulaires. Ces données suggèrent que l’intéraction de la fibuline-4 avec la tropoélastine est régulée par la présence de glycosylation, possiblement par une fonction de chaperonne dans la voie de sécrétion, et que les N-glycanes inhibent la formation de fibres élastiques dans l’espace extracellulaire.
The fibulin family is a group of eight extracellular glycoproteins, characterized by a variable number of calcium-binding epidermal growth factor (cbEGF) domains followed by a fibulin-type…
Advisors/Committee Members: Dieter Reinhardt (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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APA (6th Edition):
Lee, C. S. (2015). N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/jq085p135.pdf ; https://escholarship.mcgill.ca/concern/theses/fb494c25m
Chicago Manual of Style (16th Edition):
Lee, Chae Syng. “N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly.” 2015. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/jq085p135.pdf ; https://escholarship.mcgill.ca/concern/theses/fb494c25m.
MLA Handbook (7th Edition):
Lee, Chae Syng. “N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly.” 2015. Web. 16 Jan 2021.
Vancouver:
Lee CS. N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly. [Internet] [Masters thesis]. McGill University; 2015. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/jq085p135.pdf ; https://escholarship.mcgill.ca/concern/theses/fb494c25m.
Council of Science Editors:
Lee CS. N-glycosylation of fibulin-4 regulates tropelastin interaction and assembly. [Masters Thesis]. McGill University; 2015. Available from: https://escholarship.mcgill.ca/downloads/jq085p135.pdf ; https://escholarship.mcgill.ca/concern/theses/fb494c25m
McGill University
28.
DeGeer, Jonathan.
The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development.
Degree: PhD, Department of Anatomy and Cell Biology, 2015, McGill University
URL: https://escholarship.mcgill.ca/downloads/cf95jf05q.pdf
;
https://escholarship.mcgill.ca/concern/theses/8g84mq46p
► Le développement du système nerveux central est essentiel au bon fonctionnement physiologique. Les petites protéines G de la famille Rho sont des régulateurs clés du…
(more)
▼ Le développement du système nerveux central est essentiel au bon fonctionnement physiologique. Les petites protéines G de la famille Rho sont des régulateurs clés du cytosquelette d’actine et des microtubules, lequel est impliqué dans plusieurs aspects du développement neuronal. Les protéines de la famille Rho sont des commutateurs moléculaires qui passent d’un état actif ou inactif par association avec le GTP ou GDP, respectivement. Cet échange nucléotidique est contrôlé par des protéines régulatrices comme les facteurs d'échange de nucléotide (GEFs) qui promouvoient le remplacement du GDP par le GTP ou les «GTPase-activating proteins» (GAPs) qui catalysent l'hydrolyse du GTP en GDP. Bien que l'activation de certaines GTPases Rho contribue à la croissance et au guidage axonale, nous en savons toujours très peu sur la régulation spatiotemporelle de leurs GEFs et GAPs. Trio et CdGAP sont des régulateurs spécifiques de Rac1 et Cdc42, Trio étant une protéine Rac1GEF et CdGAP, une protéine inhibitrice pour Rac1 et Cdc42. Ces protéines sont hautement enrichies dans le cerveau des mammifères en développement. Dans cette thèse, nous avons investigué premièrement la régulation de Trio par la phosphorylation sur ses tyrosines dans le cortex embryonnaire chez le rat. Une approche in vitro a révélé que la protéine Src-kinase Fyn phosphoryle Trio sur sa tyrosine-2622, et cette modification est nécessaire pour l'activation de Rac1 en aval de nétrine-1. Ensuite, nous avons démontré que le chaperone moléculaire Hsc70 associe avec Trio et le récepteur DCC et que l'activité de la chaperone Hsc70 est nécessaire pour l’activation de Rac1 par Trio. Enfin, nous avons analysé des embryons de souris dépourvus de l’expression de CdGAP et nous avons révélé un rôle clé pour CdGAP dans le développement du système vasculaire et la cytoarchitecture des neurones corticaux. En résumé, ces études démontrent l’importance des régulateurs de Rac1 et Cdc42 au cours du développement.
The wiring of the central nervous system during development supports normal physiological function and survival, and as such occurs in a tightly regulated manner. The Rho family of small GTPases are key regulators of cytoskeletal dynamics that have been implicated in neuronal development. Rho proteins are molecular switches, cycling between an inactive GDP-bound and active GTP-bound state. Oversight of Rho GTPase nucleotide cycling is performed by regulatory proteins: guanine nucleotide exchange factors (GEFs) promote GTP-bound state, while GTP hydrolysis is catalyzed by GTPase-activating proteins (GAPs). While Rho GTPase activities contribute to axon outgrowth and guidance, little is known about the spatiotemporal regulation of their cognate GEFs and GAPs. The Rac1 GEF, Trio and Rac1/Cdc42 GAP, CdGAP are highly enriched in the developing mammalian brain. Although Trio is required for the attractive axon guidance cue netrin-1 to induce axon pathfinding, the mechanisms governing Trio function are unknown. In contrast to this, the function of CdGAP in the mammalian brain…
Advisors/Committee Members: Nathalie Lamarche (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
DeGeer, J. (2015). The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/cf95jf05q.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq46p
Chicago Manual of Style (16th Edition):
DeGeer, Jonathan. “The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development.” 2015. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/cf95jf05q.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq46p.
MLA Handbook (7th Edition):
DeGeer, Jonathan. “The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development.” 2015. Web. 16 Jan 2021.
Vancouver:
DeGeer J. The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development. [Internet] [Doctoral dissertation]. McGill University; 2015. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/cf95jf05q.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq46p.
Council of Science Editors:
DeGeer J. The regulation and function of the Rac1 GEF Trio and the Rac1/Cdc42 GAP CdGAP during neuronal development. [Doctoral Dissertation]. McGill University; 2015. Available from: https://escholarship.mcgill.ca/downloads/cf95jf05q.pdf ; https://escholarship.mcgill.ca/concern/theses/8g84mq46p
McGill University
29.
Kelley, Lyla.
The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus.
Degree: MS, Department of Anatomy and Cell Biology, 2019, McGill University
URL: https://escholarship.mcgill.ca/downloads/6t053j371.pdf
;
https://escholarship.mcgill.ca/concern/theses/z890rw670
► L'environnement nutritionnel au cours de la periode perinatale est essentiel au développement des circuits neuronaux régulant l'homéostasie énergétique et la prise alimentaire. Cet environnement est…
(more)
▼ L'environnement nutritionnel au cours de la periode perinatale est essentiel au développement des circuits neuronaux régulant l'homéostasie énergétique et la prise alimentaire. Cet environnement est modifié par la diète de la mère et en particulier, une alimentation maternelle riche en graisses (60% de gras) peut augmenter les taux de leptine circulante chez les petits et modifier les circuits impliqués dans la prise alimentaire. L'hypothalamus latéral (LH) et en particulier les neurones contenant de l'orexine-A (ORX-A) relie les noyaux hypothalamiques responsables de l'homéostasie aux neurones dopaminergiques mésocorticolimbiques qui modulent la récompense alimentaire. Cette région est sensible à la leptine chez les adultes et une exposition plus élevée à cette hormone chez les nouveau-nés pourrait modifier la sensibilité de ce noyau à la leptine. Notre étude examine l'hypothèse qu'un régime alimentaire maternel riche en graisses augmente la densité des projections neuronales des noyaux ventromédian (VMH) et dorsomédianl (DMH) de l'hypothalamus aux neurones LH ORX-A, ceux-là même qui modulent directement les cellules productrices de dopamine. Nous avons ensuite examiné la réponse intracellulaire des neurones de l'hypothalamus latéral a une injection de leptine (3mg/kg, bw, ip) chez les nouveau-nés issus de mères contrôles (CD) ou recevant une diète riche en gras (HFD). Nous avons également cherché à identifier le phenotype des populations de LH activées par la leptine exogène. Nous avons comparé les réponses des ratons issus de mères nourries avec un régime contrôle (CD) ou riche en gras (HFD) à partir du jour de gestation 13-14 jusqu'à la fin de l'allaitement. Pour évaluer les changements induits par le régime alimentaire sur la densité des afférences au LH, nous avons injecté des microbilles rétrogrades fluorescentes dans le champ LH ORX-A a 5-6 de vie postnatale. Quatre jours plus tard, nous observons une augmentation des afférences du VMH (et dans une moindre mesure du DMH) vers le LH chez les ratons HFD comparés à ceux des mères CD. Pour évaluer la sensibilité à la leptine dans l'hypothalamus latéral, nous avons mesuré la production des seconds messagers pERK et pSTAT3 par double histochimie
d'immunofluorescence dans des cellules identifiées phénotypiquement (ORX-A pour pERK, et CART et GABA pour pSTAT3). Chez les ratons HFD, nous observons une augmentation de pSTAT3 dans les neurones de LH, dont certains expriment CART. Il n'y a pas de changement dans l'activation pERK des cellules LH ORX-A. En conclusion, les changements de gras dans la diète maternelle au cours de la période périnatale ont des effets importants sur la progéniture, notamment en augmentant à la fois la densité des afférences hypothalamiques vers l'hypothalamus latéral, mais aussi en modifiant la sensibilité de ce noyau à la leptine circulante. Cet effet de programmation pourrait influencer les mécanismes de consommation de nourriture à l'âge adulte et conduire à une dysrégulation métabolique à long terme. Tous les travaux ont été financés…
Advisors/Committee Members: Claire Walker (Internal/Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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APA (6th Edition):
Kelley, L. (2019). The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus. (Masters Thesis). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/6t053j371.pdf ; https://escholarship.mcgill.ca/concern/theses/z890rw670
Chicago Manual of Style (16th Edition):
Kelley, Lyla. “The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus.” 2019. Masters Thesis, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/6t053j371.pdf ; https://escholarship.mcgill.ca/concern/theses/z890rw670.
MLA Handbook (7th Edition):
Kelley, Lyla. “The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus.” 2019. Web. 16 Jan 2021.
Vancouver:
Kelley L. The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus. [Internet] [Masters thesis]. McGill University; 2019. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/6t053j371.pdf ; https://escholarship.mcgill.ca/concern/theses/z890rw670.
Council of Science Editors:
Kelley L. The effects of a maternal high-fat diet on offspring responsiveness to leptin and afferent projections to the lateral hypothalamus. [Masters Thesis]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/6t053j371.pdf ; https://escholarship.mcgill.ca/concern/theses/z890rw670
McGill University
30.
Razi, Aida.
Role of GTPases in assembly of the bacterial 30S subunit.
Degree: PhD, Department of Anatomy and Cell Biology, 2019, McGill University
URL: https://escholarship.mcgill.ca/downloads/h415pc786.pdf
;
https://escholarship.mcgill.ca/concern/theses/vt150m265
► My PhD thesis aims to improve our understanding of the assembly process of the bacterial ribosome and the overarching goal of my research is to…
(more)
▼ My PhD
thesis aims to improve our understanding of the assembly process of the bacterial ribosome and the overarching goal of my research is to identify steps in this pathway that can be targeted with new molecular probes. Ribosome assembly in actively growing Escherichia Coli involves multiple events including synthesis of 54 ribosomal-proteins and their binding to ribosomal RNAs in a hierarchical manner. Many of these events are assisted by a number of accessory proteins known as assembly factors, making the process extremely fast and efficient. My PhD
thesis contributes new knowledge on the precise mechanism by which YjeQ and Era assist the ribosome assembly process. Recent work indicates that both factors assist the late stages of the 30S subunit assembly. To reveal the precise role of YjeQ in the context of the mature 30S subunit, we solved the structure of the 30S subunit in complex with YjeQ by cryo-electron microscopy (Cryo-EM). Our data suggested that in addition to work as a maturation factor, YjeQ also functions as a checkpoint protein testing the proofreading ability of the ribosomal subunit prior to the particle's release into the pool of actively translating ribosomes. This work provides the first example of a bacterial assembly factor that tests a specific translation mechanism of the 30S subunit. To investigate the role of Era, we used quantitative mass spectrometry (qMS), microscale thermophoresis (MST) and cryo-EM techniques. We first determined using cryo-EM the structures of the assembly intermediate that accumulated in E. coli upon depletion of Era at 3.8Å resolution. In addition, we also solved the structure of the mature 30S subunit in complex with Era. We found that Era-depleted cells accumulated three assembly intermediates at different stages of maturation ranging from early stage of maturation to the late stage of 30S subunit with missing density both in the central and 3' minor domains of the 30S subunit. Densities for ribosomal proteins (r-proteins) bS21, bS1, uS3 and uS2 bound to the central domain were also missing from the late stage of 30S subunit. The structure of the 30S subunit in complex with Era demonstrated that binding of this factor reverts the mature subunit to an immature state lacking density for the motifs integrating the decoding center. These results suggest that Era facilitates the proper folding of the platform region of the 30S subunit. In addition, Era may work as a placeholder for some of the late ribosomal proteins and prevent premature association of the 30S subunit with the 50S subunit. Finally, we tested whether YjeQ and Era exert their function in conjunction rather than independently. To this end, we obtained the cryo-EM structure of the 30S subunit in complex with Era and YjeQ at 3.5Å resolution. However, we couldn't observe any density for YjeQ in this structure. Moreover, we demonstrated Era binds to the cavity between head and platform and reverts the structure of the 30S subunit to its immature state. These results suggest that Era and YjeQ works…
Advisors/Committee Members: Joaquin Ortega (Supervisor).
Subjects/Keywords: Anatomy and Cell Biology
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APA ·
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APA (6th Edition):
Razi, A. (2019). Role of GTPases in assembly of the bacterial 30S subunit. (Doctoral Dissertation). McGill University. Retrieved from https://escholarship.mcgill.ca/downloads/h415pc786.pdf ; https://escholarship.mcgill.ca/concern/theses/vt150m265
Chicago Manual of Style (16th Edition):
Razi, Aida. “Role of GTPases in assembly of the bacterial 30S subunit.” 2019. Doctoral Dissertation, McGill University. Accessed January 16, 2021.
https://escholarship.mcgill.ca/downloads/h415pc786.pdf ; https://escholarship.mcgill.ca/concern/theses/vt150m265.
MLA Handbook (7th Edition):
Razi, Aida. “Role of GTPases in assembly of the bacterial 30S subunit.” 2019. Web. 16 Jan 2021.
Vancouver:
Razi A. Role of GTPases in assembly of the bacterial 30S subunit. [Internet] [Doctoral dissertation]. McGill University; 2019. [cited 2021 Jan 16].
Available from: https://escholarship.mcgill.ca/downloads/h415pc786.pdf ; https://escholarship.mcgill.ca/concern/theses/vt150m265.
Council of Science Editors:
Razi A. Role of GTPases in assembly of the bacterial 30S subunit. [Doctoral Dissertation]. McGill University; 2019. Available from: https://escholarship.mcgill.ca/downloads/h415pc786.pdf ; https://escholarship.mcgill.ca/concern/theses/vt150m265
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Open Access Theses and Dissertations