Mosquito saliva vital to the discovery of future drugs
Blood-feeding insects such as ticks, mosquitos and flies are widely regarded as pests given their role in disease transfer, but new research led by the University of Sydney and the Charles Perkins Centre has discovered the beneficial role of molecules produced by these bugs.
The research was published today in and led by Professor Richard Payne, an ARC Future Fellow in the Faculty of Science, and PhD candidate Emma Watson.
Best known for their transmission of the parasite that causes malaria in humans, the Anopheles mosquito has been of particular interest to lead researchers.
鈥淟ike most blood-feeding organisms, the Anopheles mosquito secretes proteins in its saliva,鈥� said Professor Payne.
鈥淭hese proteins are designed to prevent the host organism鈥檚 blood from clotting, better allowing the mosquito to access its blood-meal.鈥�
鈥淭he protein secreted in the saliva is called anophelin; it targets and binds to the central host blood coagulation enzyme thrombin, and therefore prevents blood from clotting.鈥�
Researchers were able to predict the sites on the protein where sulfate modifications were present and found that these were key for the anticoagulant activity. Once this was achieved, they were able to collect modified versions of the proteins from insect cells.
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We found that the sulfate modification of the proteins significantly enhanced the anticoagulant activity.
Only small quantities of the modified proteins could be collected from insect cells, so the research team next developed a pioneering synthetic technology to recreate the proteins in the lab in larger quantities.
鈥淲e found that the sulfate modification of the proteins significantly enhanced the anticoagulant activity. In fact, sulfated variants of anophelin exhibited a 100-fold increase in potency compared with the unmodified protein,鈥� said Emma Watson a PhD candidate in Payne鈥檚 lab and lead author on the article.
鈥淲e were also able to show that these molecules were able to dissolve blood clots in a disease model of thrombosis.
鈥淭his research lays the foundation for the development of safe anticoagulants for the treatment of thromboembolic diseases such as stroke in the future,鈥� said Professor Payne. 听
The study involved researchers from the University of Porto, the Heart Research Institute and the Australian National University, who were co-authors on the paper.
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