Largest Study of Malaria Gene Function Reveals Many Potential Drug Targets

저자：   업로드：2017-07-17  조회수：

    The creation of the aerosol can, the transfer of the Panama Canal construction to the U.S., and the formation of the CDC are all a direct result of malaria’s impact on human history, which cannot be overstated. Moreover, this single-cell parasite has been estimated to have caused the death of almost half of the world’s population since the Stone Age and has directly influenced human evolution through natural selection from diseases such as sickle cell. While this scourge on humanity has fostered some keen scientific minds and innovations, in recent years the threat of rising drug resistance has caused many malaria researchers to re-evaluate current strategies to combat his deadly disease.

    The malaria parasite's success is owed to the stripping down of its genome to the bare essential genes, scientists at the Wellcome Trust Sanger Institute and their collaborators have found. In the first ever large-scale study of malaria gene function, scientists analysed more than half of the genes in the parasite's genome and found that two thirds of these genes were essential for survival -- the largest proportion of essential genes found in any organism studied to date.

    The findings was published recently in Cell in an article entitled “Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes”.

    "This study of unprecedented scale has resulted in many more unique drug targets for malaria,” remarked Francisco Javier Gamo, Ph.D., director of the malaria unit at GlaxoSmithKline and not directly involved in the current study. “The Holy Grail would be to discover genes that are essential across all of the parasite lifecycle stages, and if we could target those with drugs it would leave malaria with nowhere to hide. The technology that the Sanger Institute has developed gives us the potential to ask those questions systematically for the first time."

    Since roughly half of the genes in the Plasmodium genome have no homologs in another organism, deciphering the parasite’s genetics has been particularly challenging. This new study, however, provides the first ever experimental evidence of function for most of those genes.

    Using a mouse model of malaria infection, Plasmodium berghei, the investigators designed a new method to decipher the function of the malaria parasite's genes. The team switched off, or knocked out, 2578 genes—more than half of the genome—and gave each knockout a unique DNA barcode. The barcoding method involves tagging specific genes with a molecular ID, enabling scientists to id

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