Groundbreaking research project may help boost vaccine development
In an innovative project with implications for malaria vaccine development, scientists have used genomics, proteomics and gene expression studies to trace how malaria parasites evolve on a molecular level as they move between their hosts and insect vectors.
That focus on the parasites’ complex life cycle is helping researchers understand when different genes switch on and off as the pathogens metamorphose through seven different life stages. In turn, that molecular-level data may benefit biomedical scientists who are identifying new targets for vaccines that would impede the parasite during stages when it is particularly vulnerable to intervention.
Hall’s group identified the gene regulation by comparing the genes expressed in the sexual stage transcriptome with the proteomes of both the sexual stage and a developmental stage in the mosquito. Several genes were identified for which transcripts were detected in the sexual stage but with protein products specific to the mosquito stage, indicating delayed translation of transcripts from these genes.
Hall says that gene-regulation motif "is particularly interesting because these proteins, expressed early in the mosquito, are the target of transmission-blocking vaccines" —that is, vaccines which raise antibodies that attack the parasite in the vector. (Such antibodies are in the "blood meal" and still work for an hour or so after the mosquito bites).
Another TIGR scientist who played an important role in the project is Associate Investigator Jane Carlton, who had led the sequencing of P. yoelii. At TIGR, Carlton constructed a composite of all three rodent genome sequences (P. yoelii, P. berghei, P. chabaudi) by aligning them against the P. falciparum genome to create a whole-genome synteny map of the four species. In collaboration with Leiden University researchers, Carlton’s group was then able to generate maps that compare the degrees of similarity among genes on P. falciparum chromosomes and its rodent-malaria counterparts.
"The paper is significant on many levels, including the integration of draft genome sequence data with microarray and protein expression data," says Carlton. "This project also shows the power of collaboration between international institutes with different areas of expertise. It was remarkably productive collaboration."
Robert Koenig | EurekAlert!
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