Protein discovery in African Trypanosomes: studying differential protein expression throughout the parasite life cycle and identification of candidate biomarkers for diagnosing Trypanosome infections
| dc.contributor.author | Eyford, Brett Alexander | |
| dc.contributor.supervisor | Pearson, Terry W. | |
| dc.date.accessioned | 2013-02-22T23:15:38Z | |
| dc.date.available | 2013-02-22T23:15:38Z | |
| dc.date.copyright | 2013 | en_US |
| dc.date.issued | 2013-02-22 | |
| dc.degree.department | Department of Biochemistry and Microbiology | |
| dc.degree.level | Doctor of Philosophy Ph.D. | en_US |
| dc.description.abstract | Research was undertaken to discover and study trypanosome proteins that may play important roles in host-parasite or vector-parasite interactions. The methods used mass spectrometry based proteomics ideally suited for analysis of low abundance molecules. First, isobaric tags were used to monitor changes in proteins expression throughout the life cycle of Trypanosoma congolense, an economically important livestock pathogen. This was the first large scale survey of protein expression in trypanosomes. In addition to generating protein expression data for approximately 2000 different parasite proteins, 6 previously undescribed T. congolense proteins were discovered. Several of the proteins with interesting expression trends were selected for molecular characterization and monoclonal antibody derivation. Second, immunoenrichment and mass spectrometry were used to identify the cognate antigen recognized by a T. congolense-specific monoclonal antibody. The antigen, a flagellar calcium binding protein, was expressed as a recombinant protein and used to test its utility as a potential serodiagnostic antigen for diagnosis of T. congolense infections. Third, a “deep-mining” protein discovery mass spectrometric method was used to identify trypanosome proteins present in the plasma of late-stage African sleeping sickness patients. A total of 254 trypanosome proteins were unequivocally identified by tandem mass spectrometry. These findings are unprecedented since never before have such a large number of pathogen proteins been discovered in human blood using a non-biased approach (i.e. without using a targeted assay). The proteins discovered provide insights into host-parasite interactions and are strong candidates as targets for new diagnostic assays. | en_US |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/4475 | |
| dc.language | English | eng |
| dc.language.iso | en | en_US |
| dc.rights.temp | Available to the World Wide Web | en_US |
| dc.subject | African trypanosomes | en_US |
| dc.subject | diagnostic biomarkers | en_US |
| dc.subject | protein expression | en_US |
| dc.subject | Trypanosoma brucei | en_US |
| dc.subject | Trypanosoma congolense | en_US |
| dc.subject | infection proteomics | en_US |
| dc.title | Protein discovery in African Trypanosomes: studying differential protein expression throughout the parasite life cycle and identification of candidate biomarkers for diagnosing Trypanosome infections | en_US |
| dc.type | Thesis | en_US |