Thesis
Leishmania mexicana phosphoproteomics
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2011
- Thesis identifier
- T12761
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Leishmania, a protozoan parasite of which there are around 30 different species, causes infections (Leishmaniasis) in millions of humans and animals around the world [1]. The leishmaniases are among the most common "neglected tropical diseases" (NTDs), threatening 350 million people and being fatal to 51,000 annually [2, 3]. Treatment of leishmaniasis primarily relies on chemotherapy, but is far from unproblematic [4-8]. The search for new treatment options has turned attention towards proteins and peptides, either as drug targets [9] or as the medical reagents [5]. The function of proteins and peptides may be greatly modulated by chemical modifications. Protein phosphorylation(s), can lead to biological responses being "turned on/off" or attenuated, making studies of phosphoproteins and protein phosphorylation patterns extremely interesting in the context of identification of potential drug targets as well as signalling pathways [10]. The current study exploited phospho-specific peptide enrichment [11, 12] and a variety of quantitative approaches, to establish a pipeline for analysis of Leishmania mexicana proteins and their phosphorylation patterns. The pipeline led to the generation of the first preliminary library of L. mexicana proteins and potential phosphoproteins, containing more than 2,000 entries. 5,127 different peptides with various potential phosphorylation sites and patterns were detected, and almost 2,000 of these validated along with their more than 2,300 phosphorylation sites (slightly redundant). Additionally, a validated list of 424 non-redundant phosphorylation sites in 107 protein kinases and 36 protein phosphatases have been constructed. Quantitative analyses were carried out at both the general and phosphoproteomics level, resulting in identification of significant life-stage as well as wild type versus kinase knock-out mutant differences. Most significant was the decreased level of protein phosphorylations in MAP kinase kinase (MKK) knock-out mutants, as well as the decreased abundance or even absence of ribosomal proteins in the amastigote life stage.
- Resource Type
- Note
- This thesis was previously held under moratorium from 9th May 2011 until 9th May 2013.
- DOI
- Date Created
- 2011
- Former identifier
- 821653
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