Solving “a long-standing mystery in malaria biology” is how researchers at the Welcome Trust Sanger Institute in Cambridge describe their recent breakthrough in malaria research.
The research group, led by Dr. Oliver Billker from the Sanger Institute and Dr. Andy Waters from Welcome Trust Centre for Molecular Parasitology at the University of Glasgow have identified a single protein, AP2-G, which acts as a “master switch” that triggers the process in the malaria parasite that spreads the disease.
The protein “is necessary for switching on genes that control the development of precursor malaria cells to the male and female forms of the parasite - the only stage that is infectious to mosquitoes.”
The discovery has important implications for malaria control strategies.
In the life cycle of the parasite, sexual reproduction can only occur in the gut of the mosquito after it has sucked the precursor parasite cells out of a person's blood.
"Current drugs treat patients by killing the sexless form of the parasite in their blood - this is the detrimental stage of the malaria lifecycle that causes illness," said Dr. Oliver Billker.
"However, it is now widely accepted that to eliminate malaria from an entire region, it will be equally important to kill the sexual forms that transmit the disease."
To confirm this, the research team silenced the AP2-G gene in the parasite and found that the manipulated parasites lost the ability to generate sexual stage parasites.
"Our studies discovered that if we switch off AP2-G in a parasite cell, then that cell cannot grow into a sexual stage parasite," said Dr. Andy Waters, co-lead author from the University of Glasgow. "This means that the parasite cannot move from the infected person back into the mosquito to continue the cycle, making transmission of that parasite from one human to another impossible."
The team also established that when the mutated gene was repaired through 'gene therapy', “the parasites regained the ability to progress to the sexual stage”. Their experiments showed that the AP2-G protein had to be in good working order for sexual stage malaria parasites to produce.
A second and separate research team led by Dr. Manuel Llinas at the Penn State University, has also successfully identified the same AP2-G protein. Papers on both these studies will appear in the next issue of Nature .
"Exciting opportunities now lie ahead for finding an effective way to break the chain of malaria transmission by preventing the malaria parasite from completing its full life cycle," said Dr Llinás. "This sexual stage bottleneck is an enticing target for interventions to prevent this comparatively small, yet critical number of sexual parasites from forming."
