In today’s Academic Minute, Dr. Natalie Spillman of Washington University in St. Louis explains research that points to an effective way to kill the microorganism that causes malaria.
Natalie Spillman is a postdoctoral researcher at Washington University in St. Louis. She was awarded her Ph.D. by the Australian National University in 2012, for research into sodium regulation in the malaria parasite. Her research project has provided a target for an entirely new class of antimalarial drugs. In mid-2012, Spillman was awarded a prestigious Amgen Fellowship from the American Australian Association and relocated to Washington University in St Louis as a postdoctoral researcher in the Howard Hughes Medical Institute lab of Prof. Daniel Goldberg.
Dr. Natalie Spillman – Killing Malaria
Cells are surrounded by membranes, which keep the insides in, and the outside surroundings out - a bit like the fence around your house. To regulate what goes in and out, cells have in their surrounding membrane molecular machines - so-called transporters - that transfer important atoms and molecules into and out of the cell. At The Australian National University, we study the transporter machinery of the single-celled malaria parasite, and one particular interest we have is in how the important biological ion sodium moves into and out of the parasite cell.
All cells maintain a low internal sodium concentration. We found that the malaria parasite uses a specialized sodium pump to drive sodium out of the cell. The malaria sodium pump is similar to pumps from fungi and other parasites, but very different to the molecular pumps that humans use. This makes it an attractive antimalarial drug target.
While we were characterizing this sodium pump, a team involving researchers in Singapore and the US had discovered a new class of antimalarial drug, the spiroindolones. However, they didn’t know the mechanism by which the drugs worked to kill the parasites. We teamed up with them, and figured out that the spiroindolone drug works by blocking the activity of the malaria parasite’s sodium pump. By blocking the pump the cells rapidly start to fill up with sodium, which then eventually leads to death of the parasite. It’s like a leaky boat that needs a pump to push the water out- if you stop the pump working, the boat fills with water and sinks. If you stop the parasite’s sodium pump working, the cell fills with sodium and the parasite dies. We went from looking at the basic biology of how the parasite gets rid of excess sodium, to realizing that it is an Achilles heel for the parasite, particularly vulnerable to attack. Hopefully, in the near future, these new spiroindolone antimalarials will become a new weapon in the global fight against malaria.
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