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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| 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 |
| 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. |
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