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Commitment to and completion of sexual development are essential for malaria parasites (protists of the genus Plasmodium) to be transmitted through mosquitoes (1). The molecular mechanism(s) responsible for commitment have [...]

The sequencing of the genome of Plasmodium falciparum promises to revolutionize the way in which malaria research will be carried out. Beyond simple gene discovery, the genome sequence will facilitate the comprehensive determination of the parasite?s gene expression during its developmental phases, pathology, and in response to environmental variables, such as drug treatment and host genetic background. This article reviews the current status of the P. falciparum genome sequencing project and the unique insights it has generated. We also summarize the application of bioinformatics and analytical tools that have been developed for functional genomics. The aim of these activities is the rational, information-based identification of new therapeutic strategies and targets, based on a thorough insight into the biology of Plasmodium spp.

Immunization with Plasmodium sporozoites that have been attenuated by [gamma]-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and humoral immune responses invoked by infected hepatocytes cells that contain long-lived, partially developed parasites. Here we analyzed sporozoites of Plasmodium berghei that are deficient in P36p (p36[p.sup.-]), a member of the P48/45 family of surface proteins. P36p plays no role in the ability of sporozoites to infect and traverse hepatocytes, but p36[p.sup.-] sporozoites abort during development within the hepatocyte. Immunization with p36[p.sup.-] sporozoites results in a protective immunity against subsequent challenge with infectious wild-type sporozoites, another example of a specifically genetically attenuated sporozoite (GAS) conferring protective immunity. Comparison of biological characteristics of p36[p.sup.-] sporozoites with radiation-attenuated sporozoites demonstrates that liver cells infected with p36[p.sup.-] sporozoites disappear rapidly as a result of apoptosis of host cells that may potentiate the immune response. Such knowledge of the biological characteristics of GAS and their evoked immune responses are essential for further investigation of the utility of an optimized GAS-based malaria vaccine. apoptosis | attenuated vaccines | host-pathogen interaction | Plasmodium

Gametocytes, the precursor cells of malaria-parasite gametes, circulate in the blood and are responsible for transmission for host to mosquito vector. Of all the malaria life cycles stages analyzed the male gametocyte has the most distinct proteome, containing many proteins involved in flagellar-based motility and rapid genome replication.

Study of the human genome helps to identify malaria-parasite receptors and molecules related to pathological processes or resistance. Multilateral initiatives and partnerships between industry and nongovernmental organization are required to ensure malaria genomics to cure affected populations.

Author(s): Edwin Lasonder [1, 2]; Yasushi Ishihama [1]; Jens S. Andersen [1]; Adriaan M. W. Vermunt [2]; Arnab Pain [3]; Robert W. Sauerwein [4]; Wijnand M. C. Eling [4]; Neil [...]

Results show that the surface protein PFS48/45 of male gametes of Plasmodium falciparum mediates fertilization process as evidenced by mutant male gamete's inability to penetrate fertile female gametes.

The circumsporozoite (CS) protein appears to be important for malaria parasites in both the vector and the host. One of the major proteins synthesized by salivary gland sporozoites, it is vital in mosquitoes for the development of sporozoites within oocysts. In the vertebrate host, it promotes sporozoite attachment to hepatocytes. These were gleaned from the creation of Plasmodium berghei lines wherein the single-copy CS gene was disrupted. Similar numbers of oocysts of comparable size were produced by the CS(-) and wild-type parasites in the mosquito midgut. However, in the CS(-) oocysts, sporozoite formation was extremely inhibited.

Targeted integration of exogenous DNA into the genome of malaria parasites will allow their phenotype to be modulated by means of gene disruption or the stable expression of foreign and mutated genes. Described here is the site-specific integration through reciprocal exchange, and subsequent expression, of a selectable marker gene into the genome of the pathogenic, bloodstage forms of the rodent malaria parasite Plasmodium berghei. Stable integration of a single copy of the marker gene (retained for more than 70 generations in the absence of drug pressure) into a nontranscribed subtelomeric repeat array of different chromosomes was observed. Expression of the gene within the subtelomeres indicated that the previously recorded absence of transcription in these regions could be due to a corresponding absence of genes rather than active silencing mechanisms., Systems enabling the genetic manipulation of malaria parasites will play a crucial role in furthering our understanding of the biology of these protozoa. In turn, this knowledge might contribute to [...]