Cracking Crystals to Fight Malaria

crystals
Malaria parasites leave behind crystals, and UCSF researchers are learning more about what guides their formation. Image by Jong Seto

For over a century, a simple test for malaria has been to smear a drop of blood between two slides and look for crystals that the parasite leaves behind.

Now UC San Francisco researchers are learning more about what guides the formation of these crystals, which could lead to new treatments for malaria.

The crystals measure one-tenth of one millimeter across and are built of iron-containing molecules called heme.

When malaria parasites infect human red blood cells and break down hemoglobin, the protein complex that transports oxygen, large amounts of heme are released into the blood stream.  But free heme is toxic to the parasites, so they pack it into crystals to sequester its toxic reactivity.

The exact molecular composition of the particles has remained mysterious until recently.

Crystals
Jong Seto, PhD

When Jong Seto, PhD, adjunct faculty in UCSF’s Department of Biochemistry and Biophysics, first imaged these particles with a high-resolution electron microscope and saw tightly packed, beautiful crystals, he remembers thinking, “There’s something really regular going on here; this packing is not just by chance.”

Seto and his collaborator, Joe DeRisi, PhD, the Albert Bowers Endowed Chair in Biochemistry and the Gordon M. Tomkins Chair at UCSF, think that malaria parasites produce a protein that binds to heme and packs it into crystals. They have found candidate proteins in the malarial genome that resemble the iron-binding human protein ferritin.

Now, Seto wants to figure out how to target these ferritin-like proteins in order to block crystal packing and release toxic heme to poison malaria.

“We would love to create an antibody against these novel proteins. If that interferes with the stacking of the crystal, it could stop malaria infection,” Seto said.