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Table of contents
ACKNOWLEDGEMENTS
TABLE OF CONTENTS
LIST OF FIGURES
LIST OF TABLES
SUMMARY
INTRODUCTION
1. Introduction to Malaria
1.1 Malaria Epidemiology
1.1.1 Malaria Disease
1.1.2 Chronicity of Malaria Infection
1.2 Current Situation and Challenges of Malaria Control
1.2.1 Drug Treatments
1.2.2 Vaccine Candidates in Development
1.2.2.1 Subunit Vaccines
1.2.2.2 Live Attenuated Parasite Vaccines
2. Etiologic Agent and Plasmodium Biology
2.1 Plasmodium Life Cycle
2.2 Parasite development in the mosquito
2.2.1 Plasmodium Sporozoites
2.3 Infection of the Mammalian Host
2.3.1 Skin Stage
2.3.2 Liver Stage
2.3.2.1 Arrest in the Sinusoid
2.3.2.2 Sinusoid Traversal
2.3.2.3 Invasion of Hepatocytes
2.3.3 Exo-erythrocytic Merozoite Formation and Release
2.3.4 Blood Stage
3. Genome organization and gene expression in P. falciparum
3.1 P. falciparum Chromosome Organization and Structure
3.2 Chromatin and its Regulation in P. falciparum
3.3 Transcription and Post-transcriptional Gene Regulation
4. Epigenetic Regulation in P. falciparum
4.1 Histone Modifications and their Writers and Eraser
4.1.1 Mechanisms of Histone Modifications
4.1.1.1 Acetylation
4.1.1.2 Deacetylation
4.1.1.3 Lysine methylation
4.1.1.4 Lysine Demethylation
4.1.2 P. falciparum Hetrochromatin Protien 1 (PfHP1) and other histone modifications readers
4.2 Nuclear Organization
4.3 Epigenetic Control of Sexual Commitment
4.4 Epigenetic Control of Hypnozoites
5. Biology and Regulation of P. falciparum Erythrocyte Membrain Protein 1 (PfEMP1)
5.1 PfEMP1 function
5.2 PfEMP1/var gene organization ans structure
5.3 Classification of adhesive domains in PfEMP1
5.3.1 Type 3 PfEMP1
5.3.2 DC4-Type PfEMP1
5.3.3 DC5-Type PfEMP1
5.3.4 DC8- and DC13-Type PfEMP1
5.3.5 var2CSA-Type PfEMP1
5.4 var gene Transcription and its Regulation
OBJECTIVES
RESULTS
ARTICLE 1 Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice.
ARTICLE 2 Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasite
ARTICLE 3 A SMYD-type methyltransferase PfSET6 associates with a subset of gene loci of Plasmodium falciparum and forms multiple cytoplasmic foci during asexual, sexual blood stage and sporozoite stage
ARTICLE 4 Analysis of the epigenetic landscape of Plasmodium falciparum reveals expression of a clonally variant PfEMP1 member on the surface of sporozoites
DISCUSSION
1. Genome-wide ChIP-seq analysis of P. falciparum sporozoites
1.1 P. falciparum sporozoites epigenome
1.2 Clonally variant gene regulation
2 varsporo expression in P. falciparum sporozoites
2.1 Adhesive properties of sporozoites and PfEMP1
2.2 Immunogenic properties
3. PfEMP1 protein expression in P. falciparum liver stage
CONCLUSION & PERSPECTIVES
BIBLIOGRAPHY
