ABSTRACT
Advances in the understanding and control of malaria depend upon knowledge of the genetic elements determining transmission and infectivity of the parasite, its response to drugs and the pathological processes of the disease (Figure 8.1). It is from knowledge of these determinants and their characterization at the molecular level that we anticipate new information about the biology of the malaria parasites and effective targets for vaccine development and drug design. These determinants and the molecular basis of their function
can often be difficult to identify. In some cases, biochemical approaches and heterologous expression in bacterial or eukaryotic cells have allowed basic characterization of Plas modium falciparum enzymes, antigens and receptors (Dobeli et al. , 1 990; Knapp, Hundt and Kupper, 1 990; Kaslow and Hill, 1 990; Creedon, Rathod and Wellems, 1 994; Chitnis and Miller 1994; Sim et al. , 1 994; Volkman, Cowman and Wirth, 1 995; Hirtzlin et al. , 1995; Luker et al. , 1 996). Even so, identification of important P. falciparum molecules and detailed characterization of their function have been subjected to limitations of in vitro culturing of parasites and contamination by host cell components (Chen and Zolg, 1987; Sherman, 1979). General cloning approaches, based on the isolation of large numbers of gene sequences by screening expression libraries with hyper-immune sera (Kemp et al. , 1983; Koenen et a!. , 1984; Hall et al. , 1984; Marchand et a!. , 1 990) or large scale sequencing of chromosome segments or cDNA from mRNA transcripts (Reddy et al. , 1993; Chakrabarti et al. , 1 994; Dame et a!. , 1 996), do not answer the important questions of function and significance of the individual gene products. Other strategies must be used to define the molecular determinants that govern parasite phenotypes.
