Protein that could halt progress of parasite-borne illnesses identified.
The protein, identified by researchers from Boston College as DOC2.1, plays a similar role in the secretion of microneme organelles that are crucial to the mobility of the parasitic protozoa Toxoplasma gondii, which causes toxoplasmosis, and Plasmodium falciparum, which causes malaria.
According to Marc-Jan Gubbels and Gabor Marth, the discovery could lead to the development of drugs that target the protein in order to block the mechanism that advances the two diseases.
"The mechanism of microneme secretion, which is required for host cell invasion, is a valid drug target," Gubbels 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,' he said.
Gubbels said that researchers in his lab obtained a temperature-sensitive mutant of Toxoplasma gondii, which displayed a mobility defect preventing it from host cell invasion.
Marth, a computational biologist, sequenced the parasite's genome and identified 33 possible sites in the genome responsible for the defect. Lab work isolated a single mutation in the DOC2.1 gene that was associated with a microneme secretion defect responsible for the mobility defect.
Manoj T. Duraisingh, co-author from the Harvard School of Public Health, generated a Plasmodium mutant wherein DOC2.1 expression could be shut off and demonstrated the protein was also crucial to microneme secretion in the parasite that causes malaria.
Gubbels said the findings reinforce the dramatic advances made possible by complete genome sequencing and computational biology, which are Marth's areas of expertise. These approaches bypass the need for the difficult and time-consuming task of mapping causative mutations by genetic crosses as used in model organisms.
"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," he added.
The study has been published in the journal Science. ( ANI )
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