Expression and behaviour of GPI-anchored surface proteins in trypanosomes
type: CreativeWork
description: There are hundreds of species in the genus Trypanosoma that proliferate in the bloodstream and tissue spaces of vertebrate hosts. African trypanosome species have evolved a variant surface glycoprotein (VSG) coat which underpins a population survival strategy based on antigenic variation. However, the vast majority of trypanosome species do not use this strategy and our understanding of the immune evasion strategies used by these species is far less developed. In some species including Trypanosoma theileri, it has been shown that the surface comprises of a mixture of a large number of different proteins, some of which are GPI-anchored. This thesis explores the expression and behaviour of trypanosome surface proteins and is split into two parts. The first part focuses on the link between the expression of VSG and the control of cellular growth in the African trypanosome species Trypanosoma brucei. The second part explores the behaviour of surface proteins in the non-African trypanosome species Trypanosoma theileri and Trypanosoma carassii. The VSG of T. brucei is GPI-anchored and is monoallelically expressed from a repertoire of hundreds of genes. The active VSG gene is located within a specialised telomeric expression site and is transcribed by RNA polymerase I. VSG is an essential protein, knockdown of the active VSG mRNA using RNAi results in a pre-cytokinesis cell cycle arrest, resulting from a threshold requirement of VSG for cellular proliferation. It is not known how the cell monitors the integrity of the VSG coat, nor how this information is relayed to the cell cycle control mechanisms. An assay was developed to determine whether an alternative GPI-anchored protein could substitute for a VSG in maintaining cell proliferation. The assay used a morpholino to knockdown VSG translation, and alone this is sufficient to produce the phenotype observed following VSG knockdown using RNAi. Since the morpholino prevents translation but leaves the VSG mRNA intact, it can…
abstract: There are hundreds of species in the genus Trypanosoma that proliferate in the bloodstream and tissue spaces of vertebrate hosts. African trypanosome species have evolved a variant surface glycoprotein (VSG) coat which underpins a population survival strategy based on antigenic variation. However, the vast majority of trypanosome species do not use this strategy and our understanding of the immune evasion strategies used by these species is far less developed. In some species including Trypanosoma theileri, it has been shown that the surface comprises of a mixture of a large number of different proteins, some of which are GPI-anchored. This thesis explores the expression and behaviour of trypanosome surface proteins and is split into two parts. The first part focuses on the link between the expression of VSG and the control of cellular growth in the African trypanosome species Trypanosoma brucei. The second part explores the behaviour of surface proteins in the non-African trypanosome species Trypanosoma theileri and Trypanosoma carassii. The VSG of T. brucei is GPI-anchored and is monoallelically expressed from a repertoire of hundreds of genes. The active VSG gene is located within a specialised telomeric expression site and is transcribed by RNA polymerase I. VSG is an essential protein, knockdown of the active VSG mRNA using RNAi results in a pre-cytokinesis cell cycle arrest, resulting from a threshold requirement of VSG for cellular proliferation. It is not known how the cell monitors the integrity of the VSG coat, nor how this information is relayed to the cell cycle control mechanisms. An assay was developed to determine whether an alternative GPI-anchored protein could substitute for a VSG in maintaining cell proliferation. The assay used a morpholino to knockdown VSG translation, and alone this is sufficient to produce the phenotype observed following VSG knockdown using RNAi. Since the morpholino prevents translation but leaves the VSG mRNA intact, it can…
author: Hambleton, Isobel
language: eng
keywords: Trypanosome, VSG
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/d6212d68-93b5-40c0-a46d-1f442a20b47a/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2022-01-15
date modified: 2026-07-22T22:24:07Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.115844