DNA Chip Helps Scientists Examine Malaria Parasites at the Exact Time they Infect Human Red Blood Cells
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| DNA |
Joseph DeRisi, Ph.D., Professor and Vice Chairman of the Department of Biochemistry and Biophysics University of California, San Francisco research improves the understanding of malaria gene regulation, particularly in the context of drug resistance. He was one of the creators of the DNA microarray known as ViroChip, which contains 20,000 snippets of vital genetic material from every known virus. He has applied this same technology to the deadliest form of the malaria parasite, Plasmodium falciparum.
P. falciparum has evolved and adapted to locations where the Anopheles mosquito co-exists with humans, resulting in a wide range of inter-strain differences in virulence and drug resistance. Dr. DeRisi developed a malaria-specific DNA chip that represents the entire genome sequence of the P. falciparum organism. He and his colleagues next grew large amounts of P. falciparum in vats of human blood. They then used the DNA chip to understand the genetic programs these parasites run at the exact time they infect human red blood cells, important findings because all the clinical symptoms of malaria occur when the parasite infects red blood cells. These findings will be applied to the development of malaria drugs and vaccines.
The life cycle of P. falciparum comprises three major developmental stages: the mosquito, liver and red blood stages. Upon red blood cell invasion, the parasite undergoes a complex series of transitions over the next 48 hours, ultimately resulting in a new population of mature malaria cells. In another NIAID supported study, Dr. DeRisi worked to detect changes in gene expression patterns among three strains of a P. falciparum and to identify biomedical pathways and mechanisms responsible for strain-specific differences. Using the malaria DNA chip, he was able to characterize DNA among the three strains during the parasite's distinctive 48-hour life cycle. This finding will help scientists identify vulnerable points in the malaria parasite’s life cycle where drugs and treatments might be especially effective.
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