Boston College researchers genetically block malaria's progression
The DOC2.1 protein plays a similar role in the secretion of microneme organelles integral to the mobility of the toxoplasmosis-causing parasitic protozoa Toxoplasmosis gondii and the malaria-causing Plasmodium falciparum. The discovery of the protein may lead to the development of drugs that target the protein to block the mechanism and stop the progression of the parasite-borne illnesses.
"The mechanism of microneme secretion, which is required for host cell invasion, is a valid drug target," Marc-Jan Gubbels, a professor of biology at Boston College, said. "Since neither microneme secretion nor invasion itself are currently targeted by any anti-malaria drugs, a potentially new class of anti-malaria reagents can be developed. The high incidence of drug resistance against malaria is a big problem, so new drugs are urgently needed."
The researchers obtained a mutant of Toxoplasmosis gondii that exhibited a mobility defect preventing it from invading host cells. Gabor Marth, a computational biologist at the university, sequenced the genome of the parasite and identified the possible sites responsible for the defect. Work in the lab isolated the single mutation in the DOC2.1 gene. Manoj T. Duraisingh, a co-author from the Harvard School of Public Health, generated a similar Plasmodium mutant wherein DOC2.1 expression could be shut off.
Using these approaches of genome sequencing and computational biology bypasses the need for time-consuming causative mutation mapping by genetic crosses.
"The re-sequencing method will permit the study of eukaryotic pathogens by forward genetics, which has shown its power in studies of model organisms, such as yeast and fruit flies," Gubbels said. "To date, many of these pathogens have limited experimental and genetic accessibility, but this roadblock can now be lifted."