Note: Intro -- Title Page -- Copyright Page -- Contents -- List of contributors -- Foreword -- Preface -- Chapter 1 Introduction: An overview of malaria and Plasmodium -- History -- The life cycle of Plasmodium -- A significant milestone in malaria research: Adaptation of Plasmodium to laboratory culture -- The advent of present-day technologies and their applications in malaria research -- Bibliography -- Chapter 2 Exoerythrocytic development of Plasmodium parasites -- The sporozoite's journey from the skin to the liver -- Sporozoite invasion -- Parasite development -- Protein export from the parasite into the host cell -- Parasite egress -- The role of innate immune responses during merosome formation -- Acknowledgments -- Bibliography -- Chapter 3 Molecular basis of erythrocyte invasion by Plasmodium merozoites -- The structure of the merozoite -- The steps of erythrocyte invasion -- Step 1: Initial attachment of the merozoite to the erythrocyte surface -- Step 2: Apical reorientation -- Step 3: Formation of the junction -- Redundancy and ligand-receptor interactions that mediate parasite adhesion during erythrocyte invasion -- Duffy binding-like family -- Reticulocyte binding-like (RBL) family -- Cooperativity between the DBL and RBL families of proteins -- Identification of novel parasite ligands -- Signaling events during erythrocyte invasion by malaria parasites -- Summary and conclusions -- Bibliography -- Chapter 4 The biology of malaria transmission -- Purpose -- History -- The current research agenda -- Biology -- Parasite -- Vector -- Vertebrate host -- Population dynamics -- Parasite dynamics in the mosquito -- Transmission-blocking interventions -- Anti-vector strategies -- Anti-parasitic transmission-blocking interventions -- Bibliography -- Chapter 5 Comparative and functional genomics of malaria parasites. , An Introduction to Plasmodium genomes -- Genome structure of malaria parasites -- Base content -- Genome size and composition -- Chromosome structure -- Lineage-specific gene families -- From genome sequences to gene function -- Genetic mapping -- Population genomics to identify vaccine or drug targets -- Global analysis of transcripts -- Epigenomics -- Reverse genetics and parasite transformation -- Summary -- Acknowledgments -- Bibliography -- Chapter 6 Gene regulation: New insights and possible intervention strategies -- Introduction -- Modes of gene regulation -- Epigenetic mechanisms of gene regulation -- Transcription factors and other DNA-binding proteins -- Alternative splicing -- Post-transcriptional, translational, and post-translational gene regulation -- Drug targeting -- Histone acetyltransferases (HATs) -- Histone deacetylases (HDACs) -- Histone methyltransferases -- Histone demethylases -- Histone kinases -- Histone post-translational modification readers -- DNA methyltransferases -- Perspectives -- Bibliography -- Chapter 7 Molecular genetic approaches to malaria research -- Transfection methods -- Transient transfection -- Stable transfection -- Bxb1 integrase system -- Genetic approaches for deriving gene function -- Single crossover integration -- Double-crossover integration -- Knockin mutations -- Engineering genetic mutations -- Forward genetic screens -- Conditional knockdown of protein function -- Cre/loxP recombinase: deletion of DNA sequences -- Tet system - conditional transcriptional regulation -- Riboenzymes: conditional transcript degradation -- FKBP DD system: conditional protein degradation -- DHFR DD system: conditional protein degradation -- Aggregation domain: conditional blockage of protein trafficking -- Protein reporters -- Localization tags -- Luciferases -- Conclusions -- Bibliography. , Chapter 8 Transcriptomics and proteomics -- Transcriptional profiling throughout the parasite life cycle -- Intraerythrocytic developmental cycle -- Sexual development and exoerythrocytic stages -- Transcriptional regulation -- Basal transcriptional machinery and transcription factors -- Promoters -- Epigenetic mechanisms -- Non-coding RNAs -- Transcriptional variation -- Variatome -- In vivo -- Transcriptional changes in response to outside stimuli -- Growth perturbations as a tool for gene annotation -- Transcription and drug resistance -- Biological insights -- Proteomics -- Translational regulation -- Post-translational modifications -- Organellar translation -- Proteome changes in response to drugs -- Conclusion -- Bibliography -- Chapter 9 The biochemistry of Plasmodium falciparum: An updated overview -- MPMP -- Carbohydrates -- Glycolysis -- Pentose phosphate pathway -- Pyruvate metabolism -- Glyoxalase metabolism -- Aminosugar metabolism -- Lipid metabolism -- Fatty acid biosynthesis -- Phosphatidylcholine -- Phosphatidylserine and phosphatidylethanolamine -- Phosphatidylinositol -- Sphingomyelin -- Isoprenoid -- Terpenoid -- Dolichol -- Glycosylphosphatidylinositols (GPIs) -- Amino acids -- Methionine and polyamine metabolism -- Arginine and proline metabolism -- Aspartate and asparagine metabolism -- Glutamate and glutamine metabolism -- Glycine and serine metabolism -- Leucine: isoleucine and valine metabolism -- Phenylalanine and tyrosine metabolism -- Lysine metabolism -- Selenocysteine -- Nucleotide metabolism -- Purine biosynthesis -- Pyrimidine biosynthesis -- Cofactors -- CoA biosynthesis -- Nicotinate and nicotinamide -- Riboflavin biosynthesis -- Thiamine (Vitamin B1) -- Pyridoxal phosphate (Vitamin B6) -- Ubiquinone biosynthesis -- Porphyrin biosynthesis -- Shikimate metabolism -- Folate metabolism -- Redox metabolism. , Mitochondrial functions -- Mitochondrial electron flow -- Mitochondrial TCA cycle -- Acetyl-CoA production in the mitochondrion -- Hemoglobin digestion and hemozoin production -- Some reflections for the future -- Bibliography -- Chapter 10 Signaling in malaria parasites -- Protein phosphorylation in Plasmodium -- Calcium-mediated signaling in Plasmodium -- Calcium homeostasis and its role in the parasite life cycle -- Calcium-dependent protein kinases and other calcium effectors in malaria parasites -- Phosphoinositide signaling and trafficking in malaria parasites -- Phosphoinositide metabolism in the parasite -- The role of phosphoinositides in the parasite life cycle -- Cyclic nucleotide signaling in the malaria parasite -- cAMP and cGMP generation in the parasite -- Role of cAMP in parasite development -- PfPKA, a major effector of cAMP signaling in the parasite -- cGMP in parasite development -- PKG, a key regulator of cGMP-mediated signaling in the parasite -- Future challenges -- Bibliography -- Chapter 11 Membrane transport proteins as therapeutic targets in malaria -- Host erythrocyte membrane: A shared ion and nutrient channel -- Parasitophorous vacuolar membrane: Protein export and solute uptake -- Protein export -- Solute exchange -- Parasite plasma membrane: Similar to other eukaryotic cells, but different -- Aquaglyceroporin -- Hexose transporter -- Digestive vacuole: A specialized lysosome‐equivalent in the parasite -- Mitochondrial inner membrane: An unusual ATP synthase with uncertain function -- Conclusions -- Acknowledgments -- Bibliography -- Chapter 12 The proteolytic repertoire of malaria parasites -- Aspartic proteases -- Plasmepsins -- Presenilin-like protease -- Cysteine proteases -- Falcipains -- Dipeptidyl aminopeptidases -- Calpain -- Serine repeat antigen (SERA) -- Metalloproteases -- Alanyl aminopeptidase -- Falcilysin. , Leucyl aminopeptidase -- Aspartyl aminopeptidase -- Methionyl aminopeptidase -- Serine proteases -- Subtilisins -- Rhomboid proteases -- Threonine proteases -- The proteasome -- Roles of proteases in parasite development -- Parasite egress and invasion of host cells -- Hemoglobin degradation -- Summary and conclusions -- Acknowledgments -- Bibliography -- Chapter 13 Development of medicines for the control and elimination of malaria -- Targets for the development of future medicines for malaria -- Drug development and the elimination agenda -- The importance of partnerships in drug discovery and development -- The process of drug development -- Combination medicines -- Identifying new antimalarial compounds -- The drug-development process -- Protecting new medicines from the emergence of resistance -- Advances in drug development made in the 21st century -- High-throughput phenotypic screening -- How fast compounds work: the parasite reduction ratio -- Pharmacokinetic and pharmacodynamic modeling -- Challenge models as proof of concept in humans -- The need for new in vitro and in vivo models for P. vivax -- The global pipeline of new medicines for treating malaria -- Next-generation endoperoxides -- Beyond the endoperoxides: overview of the pipeline -- Medicines in the broader context of malaria eradication -- Chemoprevention in vulnerable populations -- Vaccines for the chemoprevention of malaria -- Conclusion -- Acknowledgments -- Bibliography -- Chapter 14 Antimalarial drug resistance -- Background -- Treatment failure and drug resistance -- Current status -- Public health burden -- Causes of drug resistance -- Factors related to emergence -- Mechanisms of resistance -- Evolution and spread -- Detection of drug resistance -- In vivo monitoring -- In vitro sensitivity -- Molecular markers -- The future of detection -- Managing drug resistance. , Strategies for prevention.