Scientists have identified Aurora-related Kinase 1 (Ark1) as a critical enzyme that regulates the malaria parasite’s rapid multiplication.
Using Ultra Expansion Microscopy, the teams showed that depleting Ark1 disrupts spindle formation and nuclear division.
The finding opens a potential route for new drugs amid rising resistance to existing antimalarials.
Scientists from India and Britain have identified a protein that plays a central role in the malaria parasite’s ability to multiply rapidly, offering a possible new target for drugs.
The parasite Plasmodium is able to thrive in both mosquitoes and humans. It divides by a distinctive fission process that can produce several thousand progeny almost at once, and the method differs depending on whether the host is a human or a mosquito. Researchers found that one enzyme, Aurora-related Kinase 1 (Ark1), is common to both processes.
“Studies show Aurora-related Kinase 1, or Ark1, regulates parasite division in humans and mosquitoes,” said Dr Pushkar Sharma of the Biotechnology Research and Innovation Council-National Institute of Immunology (NII) in Delhi. Ark1 functions as a control switch in the parasite’s cell-division machinery. If it can be targeted by drugs, the parasite’s growth could be blocked.
To confirm Ark1’s importance, the scientists deleted or depleted the enzyme during cell division. Because Plasmodium is only about one micron in size (human hair is 50–100 microns thick), conventional imaging was difficult. A team led by Rita Tewari, professor of molecular parasitology at the University of Nottingham, used Ultra Expansion Microscopy. The technique physically expands cells to nearly five times their normal size, allowing clear visualisation of the effects of Ark1 deletion.
The experiments showed that Ark1 is produced exactly when needed during division and is essential for proper spindle formation and the correct distribution of genetic material into daughter cells in both human and mosquito stages of the parasite’s life cycle.
The work is relevant because malaria continues to show increasing drug resistance. Resistance first appeared to chloroquine and has now been observed to artemisinin. “There is a dire need for novel anti-malarial drugs,” Dr Sharma said. Protein and lipid kinases are known to be “druggable” targets for many diseases, and the new studies indicate that Ark1 belongs to this category.
The research forms part of a longer collaboration. Sharma’s group at NII has focused on signalling pathways important for infection and propagation inside human red blood cells, while Tewari’s group has examined division and development inside the mosquito. Annu Nagar, a PhD student in Sharma’s laboratory, studied Ark1’s role in the blood stage; Ryuji Yanase, Mohammed Zeeshan and others in Tewari’s group examined its function in the mosquito. Computational biologist Eelco Tromer of the University of Groningen contributed to identifying a novel Ark1-containing complex.
The studies were supported by a Team Science Grant from the Department of Biotechnology / Wellcome Trust India Alliance and by the European Research Council. The scientists now plan to map the wider network of proteins controlled by Ark1, working with Dr Keshav Prasad at NITTE University, Mangaluru, to understand more precisely how the enzyme coordinates the parasite’s unusual mode of division.
India has recorded an estimated 80–87 % reduction in malaria cases since 2015, with several regions reporting zero cases in recent years. Achieving the national elimination target by 2030 will still require continued surveillance and new tools against residual transmiss
