Plasmodium genes responsible for oocyst development and interaction with its Anopheline vector
Author(s)
Bushell, Ellen S. C.
Type
Thesis
Abstract
The transmission of the malaria parasite Plasmodium is governed by a complex
developmental cycle. This PhD thesis describes the transcriptional profiling of the
rodent malaria parasite Plasmodium berghei developmental migration through its A.
gambiae vector. The study was conducted in vivo, using a near complete P. berghei
genome microarray platform. Emphasis was placed on the oocyst stage, as little is
known about the genes implicated in the ookinete to oocyst transition, and oocyst
maturation. The data presented here provide novel transcriptional information about
Plasmodium transmission. The analysis revealed a large shift in gene utilisation as the
parasite makes its transition from the motile ookinete to the sessile oocyst.
Furthermore, this work has shown that different sets of co-regulated genes are
important for early and late oocyst development.
In addition, this PhD thesis outlines the characterisation of a novel Plasmodium
formin-like protein essential for rodent malaria transmission named the male inherited
sporulation factor important for transmission (misfit). MISFIT is expressed in the
early mosquito stages, where the protein localises to the parasite nucleus. Misfit
exhibits an absolute requirement for paternal inheritance, which is in accordance with
an observed male-biased expression pattern. pbmisfitΔ ookinetes display significant
ultrastructural and gene expression defects and fail to complete zygotic meiosis.
However, pbmisfitΔ ookinetes retain functionality and can successfully cross the
midgut epithelial barrier. In contrast, mosquito infections with pbmisfitΔ resulted in an
arrest immediately upon ookinete-oocyst transformation, where defective oocysts fail
to sporulate. An essential role in chromosome segregation during mitosis / meiosis is
postulated for MISFIT. In conclusion, the work presented in this thesis has established
the ookinete-oocyst transition as a major cell cycle check point during malaria
transmission and identified misfit as the first male inherited Plasmodium gene known
to affect development post-fertilisation.
developmental cycle. This PhD thesis describes the transcriptional profiling of the
rodent malaria parasite Plasmodium berghei developmental migration through its A.
gambiae vector. The study was conducted in vivo, using a near complete P. berghei
genome microarray platform. Emphasis was placed on the oocyst stage, as little is
known about the genes implicated in the ookinete to oocyst transition, and oocyst
maturation. The data presented here provide novel transcriptional information about
Plasmodium transmission. The analysis revealed a large shift in gene utilisation as the
parasite makes its transition from the motile ookinete to the sessile oocyst.
Furthermore, this work has shown that different sets of co-regulated genes are
important for early and late oocyst development.
In addition, this PhD thesis outlines the characterisation of a novel Plasmodium
formin-like protein essential for rodent malaria transmission named the male inherited
sporulation factor important for transmission (misfit). MISFIT is expressed in the
early mosquito stages, where the protein localises to the parasite nucleus. Misfit
exhibits an absolute requirement for paternal inheritance, which is in accordance with
an observed male-biased expression pattern. pbmisfitΔ ookinetes display significant
ultrastructural and gene expression defects and fail to complete zygotic meiosis.
However, pbmisfitΔ ookinetes retain functionality and can successfully cross the
midgut epithelial barrier. In contrast, mosquito infections with pbmisfitΔ resulted in an
arrest immediately upon ookinete-oocyst transformation, where defective oocysts fail
to sporulate. An essential role in chromosome segregation during mitosis / meiosis is
postulated for MISFIT. In conclusion, the work presented in this thesis has established
the ookinete-oocyst transition as a major cell cycle check point during malaria
transmission and identified misfit as the first male inherited Plasmodium gene known
to affect development post-fertilisation.
Date Issued
2010
Date Awarded
2010-02
Advisor
Christophides, George
Kafatos, Fotis
Vlachou, Dina
Creator
Bushell, Ellen S. C.
Publisher Department
Cell and Molecular Biology
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)