Death journey: A cell's new route
"If we can apply this knowledge to a more dangerous organism, say for example, the parasite, Plasmodium falciparum which causes malaria, we may be able to specifically activate the organism's cell death pathways without harming the host."
Dr Kevin Tan, Department of Microbiology
NOVEL PATHWAY: Dr Kevin Tan intends to identify novel activators of cell death in parasitic protozoa such as those in the malaria parasite.
NUS researchers have discovered a novel programmed cell death pathway in a single-cell parasite. In programmed cell death, the cell receives signals to die. Before this discovery, scientists have established two main pathways for this form of "cell suicide". The team's finding is the first record of the novel pathway.
The complex mechanisms involved in their cell death means that Protozoa are not as simple as we thought them to be. Indeed, they may be as complex as multicellular organisms in terms of cell death machinery, said Assistant Professor Kevin Tan of the Department of Microbiology who is the Principal Investigator for this research.
Dr Tan's Postdoctoral Fellow, Dr Nasirudeen, at the Laboratory of Molecular and Cellular Parasitology was comparing the mechanisms involved in a protozoan's programmed death with other more established multicellular systems when he stumbled upon the new pathway.
The known pathways in apoptosis of parasitic cells involve the activation of enzymes called caspases. These enzymes are responsible for the breakdown of the cell during apoptosis by cleaving numerous cellular proteins, eventually dismantling the cell completely. Besides involving caspases, programmed cell death may be caspase-independent. These caspase-independent pathways often involve the dysregulation of the membrane potential of mitochondria - components found in cells that serve as primary energy sources for all cellular functions.
The team found that despite inhibiting the action of these enzymes as well as the role played by mitochondria, the cell continues its death journey, with features suggesting another novel pathway had been activated.
Potential cure for malaria
The group's study was recently published a in Biochimie in June this year. This work, together with other work they have been doing that led to this discovery will be featured as an article in the December 2005 issue of Trends in Parasitology.
The team has been working on Blastocystis hominis, which is an intestinal protozoan parasite, as a model for protozoan cell death. It is transmitted through the fecal-oral route and is prevalent in areas with poor hygiene. "But if we can apply this knowledge to a more dangerous organism, say for example, the parasite, Plasmodium falciparum which causes malaria, we may be able to specifically activate the organism's cell death pathways without harming the host," said Dr Tan.
The NUS team is currently working with members of NTU's School of Biological Sciences to identify key activators of malaria cell death using microarray technology. If malaria parasites can be induced to commit suicide, this would be good news for clinicians. Currently, there are no effective vaccines for the disease. And the disease has through time, become resistant to most antimalarial drugs.
"We need new avenues for anti-malaria therapy. Perhaps five to 10 years down the road, and with sufficient funding, we can find a new cure for malaria as well as prevention of other parasitic diseases, using our knowledge on the pathways of programmed cell death," said Dr Tan.