Malaria remains a global scourge to human life and existence responsible for up to 500 million cases and 3 million deaths annually. Currently there is no feasible and effective vaccine against these parasites and widespread drug resistance to numerous malaria chemotherapeutics has bolstered the need to design and establish novel malaria drug and vaccine strategies. An avenue for such discovery occurred in October 2002 with the landmark publication of the complete genome of Plasmodium falciparum, the most debilitating of malaria in humans. Given the vast wealth of information provided by such large-scale sequencing projects, it is essential that current annotations and predicted gene structures be accurate when presented to the malaria research community at large. As with all current genome projects, the gene predictions present in the P. falciparum and P. yoelii yoelii (rodent malaria) genomes need to be enhanced using pre-existing genomics-based datasets and the targeted sequencing of new cDNA clones. This project will focus on improving and manually curating the published P. y. yoelii gene annotations such that malaria researchers and vaccine developers can more accurately identify novel vaccine and drug targets using correct gene structures. All information gained from this project will be directly communicated to the scientific research community and displayed publicly using the online malaria genome resource, PlasmoDB. This project will utilize basic bioinformatics, comparative genomics and established large-scale experimental datasets to manually curate and improve the annotated P. falciparum and P. y. yoelii gene structures, particularly the delineation of exon/intron boundaries. Substantial expressed sequencing tag (EST) sequencing data (>20,000 total sequences) for P. y. yoelii will be compared to the current malaria gene predictions to validate exon junctions and identify open reading frames (ORFs) not present in the original gene annotations. Furthermore, post-genomic technologies including microarray and proteome analysis will be used to verify gene structures. Finally, selected gene structures will be determined using targeted cDNA cloning and sequencing. Knowledge gained from this research will lead to understanding of the complex biology of malaria parasites and improve comprehension of the intracacies associated with pathogen genomes. ? ? ?
