Abstract
Genome manipulation, the primary tool for assigning function to sequence, will be essential for understanding Plasmodium biology and malaria pathogenesis in molecular terms. The first success in transfecting Plasmodium was reported almost ten years ago. Gene-targeting studies have since flourished, as Plasmodium is haploid and integrates DNA only by homologous recombination. These studies have shed new light on the function of many proteins, including vaccine candidates and drug resistance factors. However, many essential proteins, including those involved in parasite invasion of erythrocytes, cannot be characterized in the absence of conditional mutagenesis. Proteins also cannot be identified on a functional basis as random DNA integration has not been achieved. We overview here the ways in which the Plasmodium genome can be manipulated. We also point to the tools that should be established if our goal is to address parasite infectivity in a systematic way and to conduct refined structure-function analysis of selected products.
Highlights
It is safe to predict that the wealth of information revealed by the sequence of the Plasmodium falciparum genome will benefit many areas of malaria research (Waters and Janse, 2004)
On the one hand, understanding the function of a given gene is straightforward, and we should soon have the tools for manipulating any gene
Identification of genes based on their function is still problematic
Summary
It is safe to predict that the wealth of information revealed by the sequence of the Plasmodium falciparum genome will benefit many areas of malaria research (Waters and Janse, 2004). New drug targets will be identified by capitalizing on the comprehensive view of parasite metabolism, as was already done to demonstrate the antimalarial activities of fosmidomycin and triclosan (Jomaa et al, 1999; Surolia and Surolia, 2001). Another much anticipated impact of the genome sequence is on vaccine development, via the formulation of new ‘vaccinomic’ approaches (Hoffman et al, 1998; 2002). Apicomplexa are part of one of the most ancient eukaryotic lineages, phylogenetically distant from the model organisms already sequenced They have unique structural features and have evolved distinct solutions to basic problems; for example they divide by multiple fission, locomote by gliding and induce the formation of new membrane
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