Malaria cases are rising, prompting the World Health Organisation to call for new treatments to combat this global health challenge.
Transmitted by infected mosquitoes, malaria is most common in tropical and subtropical regions. As the parasite evolves, research is critical to developing more effective treatments.
Researchers from the Centre for Innovation in Infectious Disease and Immunology Research (CIIDIR), a partnership between Barwon Health and Deakin University’s Institute for Mental and Physical Health and Clinical Translation (IMPACT) are leading the research. Together, they’re working to better understand malaria’s biological pathways and identify new treatment strategies.
In a recent study, PhD candidate Mitchell Trickey and Professor Tania de Koning-Ward investigated how specific proteins support malaria parasite survival by examining the pathways they use to absorb nutrients.
Understanding malaria and its survival mechanisms
The malaria parasite has a complex lifecycle, involving both human and mosquito hosts. When an infected mosquito bites a human, the parasite enters the bloodstream and travels to the liver, where it multiplies. It then infects red blood cells, using specialised channels called new permeation pathways (NPPs) to access nutrients essential for survival.
NPPs are channels created by the parasite that allow nutrients to pass through the outer membrane of infected red blood cells. These pathways are linked to a protein complex called RhopH, which includes a group of proteins known as RhopH1/CLAG.
Targeting key proteins for new treatments
Mr Trickey’s research revealed that a group of proteins in malaria parasites named “CLAG” proteins, can be split into two distinct groups that have separate and non-complementary functions.
Additionally, his research revealed that an individual CLAG protein he terms “CLAGX” in a rodent malaria model has the same function as the human malaria protein “CLAG3”.
‘Our research provided the first evidence that the CLAGX protein in rodent malaria is in fact the functional equivalent of CLAG3 in human malaria, and this has helped us better understand the proteins essentiality.’
His research also provided the first functional evidence that these CLAG proteins are essential to the malaria parasites ability to absorb nutrients and are critical to its survival.
‘The CLAG proteins are an exciting candidate for a drug target, which could potentially be used to disrupt the absorption of nutrients through NPPs, starving the parasite and stopping the progression of the disease,’ he explained.
Mr Trickey says that these results are highly encouraging, supporting further research into CLAG proteins as potential targets for new malaria drugs and vaccines.
‘The development of new drugs to treat individuals infected with malaria, or a vaccine to prevent infections from occurring is critical in the global fight against the disease which kills 600,000 people each year worldwide’ he says.
Malaria research at Deakin University
Professor de Koning-Ward’s laboratory continues to investigate essential malaria parasite proteins as potential targets for new drug treatments and vaccine development.
Recently, Professor de Koning ward was awarded a National Health and Medical Research Council (NHMRC) grant to further investigate how malaria parasites establish a communication pathway within infected red blood cells to ensure their survival. This ongoing research into the parasite’s biology is crucial for developing effective treatments.
