Utilising Yeast as a Model Organism to Deconstruct the Regulation of Tumour Associated Lipogenesis
type: CreativeWork
description: It is important for cells to respond to external signals. Central to these responses are the sensing and signalling pathways that communicate with the nucleus and facilitate necessary changes in gene expression. Of particular importance are the mitogen-activated protein kinase (MAPK) and the mammalian target of rapamycin (mTOR) pathways. Both of these pathways have been shown to be involved in cell growth, proliferation, motility and survival. They are under intensive investigation in connection with cancer with recent evidence suggests their role in mediating lipogenesis. Lipogenesis accompanies a variety of disease states, including the formation of brain tumours. Malignant brain tumours are rapidly growing and often invade surrounding healthy tissue, resulting in poor prognosis for the patient. The ability to limit tumour growth and reduce invasion through a better understanding of tumour associated lipid formation may offer targets for the development of new therapies. Yeast is frequently used as a paradimic organism for the study of human diseases. In this study a Nile red assay has been developed, optimised and validated to measure levels of both polar and neutral lipids within yeast cells. This method has been utilised in the yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe, to study the role of the MAPK pathways in regulating lipid accumulation. Data in this thesis demonstrates that stress-activated protein kinase pathways (SAPK) play a key role in regulating lipid accumulation upon nitrogen limitation, as cells enter the stationary phase of growth. Evidence from S. cerevisiae proposes that the lipogenic switch occurs in two phases, with the central MAPK (Hog1) activated in both a MAPKK (Pbs2) independent and dependent manner. Analysis of Hog1 phosphorylation during various growth phases, suggests that there are previously uncharacterised sites on Hog1 which are potentially phosphorylated during phase one by the protein kinase Sch9, a ta…
abstract: It is important for cells to respond to external signals. Central to these responses are the sensing and signalling pathways that communicate with the nucleus and facilitate necessary changes in gene expression. Of particular importance are the mitogen-activated protein kinase (MAPK) and the mammalian target of rapamycin (mTOR) pathways. Both of these pathways have been shown to be involved in cell growth, proliferation, motility and survival. They are under intensive investigation in connection with cancer with recent evidence suggests their role in mediating lipogenesis. Lipogenesis accompanies a variety of disease states, including the formation of brain tumours. Malignant brain tumours are rapidly growing and often invade surrounding healthy tissue, resulting in poor prognosis for the patient. The ability to limit tumour growth and reduce invasion through a better understanding of tumour associated lipid formation may offer targets for the development of new therapies. Yeast is frequently used as a paradimic organism for the study of human diseases. In this study a Nile red assay has been developed, optimised and validated to measure levels of both polar and neutral lipids within yeast cells. This method has been utilised in the yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe, to study the role of the MAPK pathways in regulating lipid accumulation. Data in this thesis demonstrates that stress-activated protein kinase pathways (SAPK) play a key role in regulating lipid accumulation upon nitrogen limitation, as cells enter the stationary phase of growth. Evidence from S. cerevisiae proposes that the lipogenic switch occurs in two phases, with the central MAPK (Hog1) activated in both a MAPKK (Pbs2) independent and dependent manner. Analysis of Hog1 phosphorylation during various growth phases, suggests that there are previously uncharacterised sites on Hog1 which are potentially phosphorylated during phase one by the protein kinase Sch9, a ta…
author: Rostron, Kerry
language: en
date published: 2015-05
date modified: 2026-07-24T01:35:53Z
provider: University of Central Lancashire
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Central Lancashire