Scrutinizing a Killer

Malaria infected human red blood cell, ring stage. Image taken by Dr. Cathie Magowan
with the x-ray microscope at the Center for X-Ray Optics, Lawrence Berkeley National Laboratory

Using one of the most advanced microscopes in the world, a researcher observes the life cycle of the one of the world’s most deadly diseases. She can see, as even the human immune system cannot, the progress of a malaria parasite, Plasmodium falciparum.

The researcher is Cathie Magowan, a biologist who is using the x-ray microscope at the Center for X-Ray Optics (CXRO) at the Advanced Light Source, part of Lawrence Berkeley National Laboratory. At the CXRO, Magowan is obtaining views never before seen of the malaria parasite during its life cycle. Until now, the malaria parasite has not been seen with such high resolution in an intact red blood cell. “I’m able to observe the malaria parasite much more closely than I could with a light microscope. By light microscopy, I could see the parasite and discern some structure, but now I can observe parasite morphology and development within the intact red blood cell at much higher resolution.” Magowan and colleagues are recording a 48-hour cycle of the parasite at work, with images taken every six hours.

A means of viewing the life cycle of the malaria parasite–its procedures in attacking and infesting healthy red blood cells–could help researchers visualize the junctures at which the parasite could be targeted for chemotherapy. Such views would help, too, by showing a parasite that is unaffected by treatment compared to one that is.

Magowan could use several types of microscope in her work, such as a light microscope, which uses the visible spectrum of light energy, or microscopes that use invisible energy, such as scanning probe, electron, or x-ray microscopes. Light microscopes can use living specimens–a profound advantage in biological research–but have a limited resolution. Scanning probe microscopes provide closer views than light microscopes but show only the surface of a sample, without contrast or depth. Electron microscopes can penetrate a sample and provide very powerful magnification. However, biological samples must be encased in resin and sectioned before viewing, so they cannot be living when viewed with these microscopes.

X-ray microscopes, however, have the advantages of both types of microscopes. They can use living or hydrated samples, instead of samples that are dried or in a vacuum. With the x-ray microscope, Magowan simply applies a droplet of the sample to a specially designed silicon nitride membrane, and puts it under the microscope.

Also, the images shown with the x-ray microscope are not limited to the surface of the sample. Contrast is possible because x-rays transmitted through the sample interact with one another. In a living sample, such as a red blood cell, depth can be shown by using x-ray wavelengths that are absorbed in the water in the cell as the x-ray passes through.

The CXRO staff has used state-of-the-art technology adopted from light microscopes to build in precision controls not found in other x-ray microscopes. For instance, Werner Meyer-Ilse and Hector Medecki of CXRO developed a “mutual indexing system” for locating the viewing target, which is no small problem with an area as small as a single-celled organism.

What you have in your mind?