Characterization of sexual commitment and the early steps of sexual development in the human malaria parasite Plasmodium falciparum

Transmission of malaria requires that some parasites abandon asexual replication and develop into sexual stages termed gametocytes. The discovery of the transcription factor PfAP2-G as the master regulator of sexual conversion has boosted our understanding of sexual development. The pfap2-g locus is...

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Detalles Bibliográficos
Autor: Llorà Batlle, Oriol
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/668323
Acceso en línea:http://hdl.handle.net/10803/668323
Access Level:acceso abierto
Palabra clave:Malaria
Plasmodium falciparum
Gametocytes
Sexual conversion
PfAP2-G
Heterochromatin nucleation
Malària
Gametòcits
Conversió sexual
Nucleació d'heterocromatina
579
Descripción
Sumario:Transmission of malaria requires that some parasites abandon asexual replication and develop into sexual stages termed gametocytes. The discovery of the transcription factor PfAP2-G as the master regulator of sexual conversion has boosted our understanding of sexual development. The pfap2-g locus is controlled by heterochromatin-based silencing, with only a few parasites activating the locus and committing to sexual development at each asexual cycle. How heterochromatin forms in pfap2-g is currently unknown. Moreover, the initial steps of sexual conversion after pfap2-g activation, together with the biology of sexually committed stages, remain poorly characterized. In this thesis, we identified a new route of sexual conversion involving direct conversion within the same cycle of initial PfAP2-G expression. We also developed a conditional activation system for PfAP2-G, achieving synchronous sexual conversion of the majority of parasites, which enables the characterization of sexually committed parasites and early sexual stages. Finally, in an attempt to elucidate the mechanisms behind heterochromatin formation in pfap2-g, we gained insight into the role of different elements in heterochromatin nucleation.