Advances in Malaria Research

Deepak Gaur, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India. Chetan Chitnis, International Centre for Genetic Engineering and Biotechnology, New Delhi, India; Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France. Virander S. Chauhan is Director for the International Centre for Genetic Engineering and?Biotechnology, New Delhi Component. Dr. Chauhan's research focuses on Malaria vaccine and drug development. Dr. Chauhan has written numerous articles related to the Fields of malarial biology and drug discovery. Dr. Chaudan is also co-editor of Recombinant and Synthetic Vaccines (Springer 1995).

List of contributors xiii Foreword xvii Preface xix 1 Introduction: An overview of malaria and Plasmodium 1 Virander S. Chauhan, Chetan E. Chitnis, and Deepak Gaur History 1 The life cycle of Plasmodium 3 A significant milestone in malaria research: Adaptation of Plasmodium to laboratory culture 4 The advent of present-day technologies and their applications in malaria research 5 Bibliography 6 2 Exoerythrocytic development of Plasmodium parasites 9 Volker T. Heussler, Annika Rennenberg, and Rebecca R. Stanway The sporozoite's journey from the skin to the liver 10 Sporozoite invasion 14 Parasite development 15 Protein export from the parasite into the host cell 20 Parasite egress 23 The role of innate immune responses during merosome formation 26 Acknowledgments 27 Bibliography 27 3 Molecular basis of erythrocyte invasion by Plasmodium merozoites 33 Deepak Gaur, Chetan E. Chitnis, and Virander S. Chauhan The structure of the merozoite 39 The steps of erythrocyte invasion 41 Redundancy and ligand-receptor interactions that mediate parasite adhesion during erythrocyte invasion 57 Signaling events during erythrocyte invasion by malaria parasites 74 Summary and conclusions 75 Bibliography 75 4 The biology of malaria transmission 87 Robert E. Sinden Purpose 87 History 87 The current research agenda 88 Biology 88 Population dynamics 106 Transmission-blocking interventions 110 Bibliography 114 5 Comparative and functional genomics of malaria parasites 125 Martine M. Zilversmit, Sittiporn Pattaradilokrat, and Xin-zhuan Su An Introduction to Plasmodium genomes 125 Genome structure of malaria parasites 127 From genome sequences to gene function 133 Summary 139 Acknowledgments 139 Bibliography 139 6 Gene regulation: New insights and possible intervention strategies 149 Artur Scherf, Nicholas A. Malmquist, Rafael M. Martins, Shruthi S. Vembar, and Jose-Juan Lopez-Rubio Introduction 149 Modes of gene regulation 150 Drug targeting 164 Perspectives 169 Bibliography 171 7 Molecular genetic approaches to malaria research 179 Brendan Elsworth, Mauro F. Azevedo, Brendan S. Crabb, and Paul R. Gilson Transfection methods 179 Genetic approaches for deriving gene function 184 Conditional knockdown of protein function 187 Protein reporters 190 Conclusions 192 Bibliography 192 8 Transcriptomics and proteomics 197 Archana P. Gupta, Zbynek Bozdech, and Peter R. Preiser Transcriptional profiling throughout the parasite life cycle 198 Transcriptional regulation 201 Transcriptional variation 205 Biological insights 208 Proteomics 208 Translational regulation 209 Conclusion 212 Bibliography 212 9 The biochemistry of Plasmodium falciparum: An updated overview 219 Hagai Ginsburg MPMP 219 Carbohydrates 219 Lipid metabolism 227 Amino acids 240 Nucleotide metabolism 252 Cofactors 256 Redox metabolism 265 Mitochondrial functions 268 Hemoglobin digestion and hemozoin production 273 Some reflections for the future 276 Bibliography 277 10 Signaling in malaria parasites 291 Pushkar Sharma and Sudhir Kumar Protein phosphorylation in Plasmodium 291 Calcium-mediated signaling in Plasmodium 292 Phosphoinositide signaling and trafficking in malaria parasites 295 Cyclic nucleotide signaling in the malaria parasite 296 Future challenges 300 Bibliography 300 11 Membrane transport proteins as therapeutic targets in malaria 307 Sanjay A. Desai, Kempaiah Rayavara, Paresh Sharma, Sayeed K. Syed, Wang Nguitragool, and Praveen Balabaskaran Nina Host erythrocyte membrane: A shared ion and nutrient channel 308 Parasitophorous vacuolar membrane: Protein export and solute uptake 311 Parasite plasma membrane: Similar to other eukaryotic cells, but different 314 Digestive vacuole: A specialized lysosome-equivalent in the parasite 316 Mitochondrial inner membrane: An unusual ATP synthase with uncertain func