About the Project

Mosquitoes transmit many diseases, including Zika and malaria. Malaria alone is responsible for about two hundred million clinical cases worldwide and kills nearly one million people each year. Malaria is caused by Plasmodium parasites that are transmitted by anopheline mosquitoes. Zika can trigger paralysis and birth defects. Inhibiting pathogen development in mosquitoes will block disease transmission. My research aims to find target genes that are essential for pathogen transmission in mosquitoes. Moreover, we develop drugs targeting these critical genes to stop disease transmission.

By genomic approaches, we discovered that the fibrinogen-related protein 1 (FREP1) is critical for malaria parasite infection in Anopheles gambiae and facilitates Plasmodium invasion in mosquitoes through interacting with gametocytes and ookinetes. Furthermore, we test the hypothesis that small molecules disrupting this interaction will prevent parasites from infecting mosquitoes. We screened a fungal extract library and obtained a candidate fungal extract of Aspergillus niger that specifically inhibited the interaction between FREP1 and Pfalciparum infected erythrocytes by about 92%. Notably, feeding mosquitoes with the candidate fungal extract significantly inhibited P. falciparum infection in the mosquito midgut. A bioactive compound that prevents FREP1 from binding to gametocytes or ookinetes was isolated and identified as P-orlandin, which is neither cytotoxic nor inhibiting the development of P. falciparum gametocytes or ookinetes. Importantly, P-orlandin significantly reduced P. falciparum infection intensity in mosquitoes. In summary, we discovered FREP1 as a key gene to mediate malaria transmission. Disruption of the interaction between FREP1 and parasites effectively reduces Plasmodium infection in mosquitoes. Targeting FREP1 with small molecules is thus an effective novel approach to block malaria transmission.

Project Info

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