Advances in Malaria Research (eBook)

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 function 318

Conclusions 319

Acknowledgments 319

Bibliography 319

12 The proteolytic repertoire of malaria parasites 325
Puran Singh Sijwali and Philip J. Rosenthal

Aspartic proteases 325

Cysteine proteases 330

Metalloproteases 333

Serine proteases 335

Threonine proteases 338

Roles of proteases in parasite development 340

Summary and conclusions 343

Acknowledgments 343

Bibliography 343

13 Development of medicines for the control and elimination of malaria 353
Jeremy N. Burrows and Timothy N. C. Wells

Targets for the development of future medicines for malaria 356

The process of