Researchers at Weill Cornell Medicine shed new light on malaria infection, one of the world’s largest public health challenges. Malaria kills young children every two minutes-more than any other infection.
Plasmodium falciparum is the most prevalent and deadly malaria parasite, which is transmitted by mosquitoes and has a complex life cycle. Symptoms of malaria occur when the asexual stage of the parasite begins to replicate in the red blood cells. However, these asexual forms must change to the male and female stages, called gamete mother cells, in order to infect the disease-spreading mosquitoes.
and Study published on January 27 Researchers at Nature Microbiology report that researchers at Weill Cornell Medicine have identified a protein called HDP1 that plays an important role in the activation of genes required for the development of these male and female stages. This discovery provides important new insights into how parasites control this conversion to gamete mother cells.
“HDP1 is essential for the development of the infectious stage of the parasite,” said the senior author. Bjorn KafsakAssociate Professor of Microbiology and Immunology at Weill Cornell Medicine.
Previous research Switching between different stages indicates that the master gene regulator AP2-G, which initiates the development of transmissible stages by activating other regulators of gene expression, including HDP1, is required.
In their new study, researchers have shown that HDP1 is required for parasites to mature to the stage of gamete mother cells. This is the first time such a relationship has been shown. They used CRISPR / Cas9 gene editing technology to remove the HDP1 gene in Plasmodium falciparum. Using microscopy and other techniques, they were able to discover at the molecular level what was happening inside these cells.
They found that without HDP1, parasites could not increase the expression of the genes needed to assemble mature gamete mother cells and give them a characteristic sickle shape. This ultimately leads to the death of these gamete mother cells, making them incapable of infecting mosquitoes.
“HDP1 is the first of a previously uncharacterized class of DNA-binding proteins identified in malaria,” said leading author Riward Campelo Morillo, a researcher in microbiology and immunology. Cuffsack Lab.. “It provided us with a deeper understanding of how genes are regulated in these parasites.”
The team aims to further study how these molecular changes cause parasites to take the form of a sickle, but this is still unknown.
“Understanding the development programs for these stages of infection may ultimately lead to the potential of future drugs to stop the infection,” Kafsack said. “We may be able to find additional components of this process that are unique to these parasites and target them with drugs.”
Julie Grisham is a freelance writer for Weill Cornell Medicine.
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