Identification of M-RAS/RAS-2 expression patterns in Caenorhabditis elegans and characterization of M-RAS/RAS-2-null worms
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Gunaretnam, Erandika Prasadani
issued: 2014-06-18T16:03:35Z
issued: 2014
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: M-Ras is a member of the Ras superfamily of small-molecular weight-GTP binding proteins. It is a close relative of the oncoprotein p21Ras and shares 50% overall amino acid sequence identity. ras-2 is the Caenorhabditis elegans ortholog of the human M-Ras. It shows strong conservation of structure in worms and vertebrates. In mammals, endogenous M-Ras acts downstream of the EGF and FGF receptors to activate ERK (MAPK) signaling. The M-Ras is predominantly expressed in the mammalian central nervous system and the heart. Many human cancers including breast and colonic cancers exhibit dramatic elevations of M-Ras mRNA. Receptor tyrosine kinase /RasGTPase/ERK signaling pathway is evolutionary conserved. In C. elegans this highly conserved signaling pathway controls many biological processes including vulval induction. C. elegans is a good model system to understand the role of M-Ras in RTK/Ras/ERK pathway. To understand the expression patterns of RAS-2 in C. elegans, I generated a transgenic C. elegans that expresses GFP driven by the endogenous ras-2 promoter. To investigate the effect of over expressed or activated RAS-2, I also generated transgenic lines over expressing WT or activated RAS-2. I observed that RAS-2 is expressed in various tissues and organs of C. elegans including amphid sensory apparatus, proximal myoepithelial sheaths, spermatheca and in developing gonads. Based on the ras-2 expression patterns, I chose and performed appropriate behavioral assays to characterize ras-2 null worms. The phenotypic characterization and behavioral observations on ras-2 null worms revealed several phenotypes including smaller body size and faster locomotion. Furthermore, based on the behavioral assays, I found that ras-2 mutants have a normal ability to sense inputs and reproduce. To investigate the importance of RAS-2 in pathological signaling of activated LET-23 (EGFR) or activated LET-60 (p21Ras) which cause multivulval phenotype in C. elegans, I examined the different …
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/47019
note: IDENTIFICATION OF M-RAS/RAS-2 EXPRESSION PATTERNS IN CAENORHABDITIS ELEGANS AND CHARACTERIZATION OF M-RAS/RAS-2-NULL WORMS by ERANDIKA PRASADANI GUNARETNAM B.V.Sc., The University of Peradeniya, Sri Lanka, 2009 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2014 © Erandika Prasadani Gunaretnam 2014 ii ABSTRACT M-Ras is a member of the Ras superfamily of small-molecular weight-GTP binding proteins. It is a close relative of the oncoprotein p21Ras and shares 50% overall amino acid sequence identity. ras-2 is the Caenorhabditis elegans ortholog of the human M-Ras. It shows strong conservation of structure in worms and vertebrates. In mammals, endogenous M-Ras acts downstream of the EGF and FGF receptors to activate ERK (MAPK) signaling. The M-Ras is predominantly expressed in the mammalian central nervous system and the heart. Many human cancers including breast and colonic cancers exhibit dramatic elevations of M-Ras mRNA. Receptor tyrosine kinase /RasGTPase/ERK signaling pathway is evolutionary conserved. In C. elegans this highly conserved signaling pathway controls many biological processes including vulval induction. C. elegans is a good model system to understand the role of M-Ras in RTK/Ras/ERK pathway. To understand the expression patterns of RAS-2 in C. elegans, I generated a transgenic C. elegans that expresses GFP driven by the endogenous ras-2 promoter. To investigate the effect of over expressed or activated RAS-2, I also generated transgenic lines over expressing WT or activated RAS-2. I observed that RAS-2 is expressed in various tissues and organs of C. elegans including amphid sensory apparatus, proximal myoepithelial sheaths, spermatheca and in developing gonads. Based on the ras-2 expression patterns, I chose and performed appropriate behavioral assays to characterize ras-2 …
has type: Thesis/Dissertation
date issued: 2014-09
is shown at: 10.14288/1.0167494
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 2.5 Canada
rights URI: http://creativecommons.org/licenses/by-nc-nd/2.5/ca/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/47019