Indian scientists may have found a way to stop malaria | Pune News

Pune: It’s a disease that has haunted civilizations, from the ancient Greeks to the Chinese. It killed even the first farmers in the neolithic age, 10,000 years ago. By the 20th century, malaria was responsible for 5% of all human deaths.What makes the malaria parasite, Plasmodium, particularly dangerous is its ability to thrive in insects and vertebrate hosts, two completely different species. It’s a master of adaptation: in mosquitoes, it leeches off nutrients; in humans, it can evade immune defences, and multiply quickly.For years, researchers have looked for weaknesses in Plasmodium. Now, scientists from India and Britain may have struck gold, with the discovery of a protein they believe can be exploited to stop Plasmodium from multiplying, essentially blocking the disease.

In all organisms, cell division is the most fundamental process for development. Plasmodium uses a unique “fission” method that produces several thousand progeny almost instantaneously. If that wasn’t enough, the parasite also divides differently depending on the host, human or a mosquito.But there’s one common thread, an enzyme known as ‘Ark1’. “Studies show Aurora-related Kinase 1, or Ark1, regulates parasite division in humans and mosquitoes,” said Dr Pushkar Sharma, from the Biotechnology Research and Innovation Council-National Institute of Immunology, Delhi.Put simply, Ark1 acts like a “control switch” in Plasmodium’s cell-division process. If drugs can be designed to target Ark1, the parasite’s growth could be controlled, the scientists said.

To arrive at the decision that Ark1 was key for the parasite’s survival, the scientists had to first delete or deplete it during Plasmodium’s cell-division process. But the second step, monitoring the parasite’s growth after deletion, threw up a problem.Plasmodium can be as small as one micron; the thickness of human hair is 50-100 microns. It was difficult to even image properly.A cutting-edge solution came from the second team, in Britain, led by Rita Tewari, a molecular parasitologist and a professor at the School of Life Sciences, University of Nottingham.“We used Ultra Expansion Microscopy, a relatively new technique in malaria research, which involves physical expansion of cells to almost five times their normal size. This let us image the impact of Ark1 deletion,” Tewari said.What the scientists found was that Ark1 was produced by Plasmodium at exactly the moment it was needed during cell division, playing the most crucial role in dividing the malarial parasite. Secondly, they discovered its ability to regulate “spindle formation” and nuclear division — basically dividing the genetic matter correctly into two cells — in both humans and mosquitoes.The breakthrough, the scientists said, could help humanity develop new drugs against malaria, which is, worryingly, also showing signs of increasing drug resistance. “Signs first emerged of chloroquine resistance. We have now noticed artemisinin resistance too. There is a dire need for novel anti-malarial drugs,” Dr Sharma saidHe added that protein and lipid kinases are known to be very “druggable” targets for various diseases. “These enzymes are attractive candidates to target malaria parasites, which is also exemplified by our studies,” he said.Next, the scientists aim to map the broader network of proteins controlled by Ark1, hoping to better understand how the parasite coordinates its unusual mode of division. “We are trying to figure out the mechanisms via which Ark1 plays such a critical role in parasite biology by using modern approaches in collaboration with Dr Keshav Prasad at NITTE University, Mangaluru,” said Dr Sharma.How two teams worked togetherThis research against malaria is part of an ongoing quest by two groups — Dr Sharma’s team at NII and Tewari’s at University of Nottingham — to delineate signalling mechanisms involved in the development of malaria parasite. The Tewari group has been investigating the process of division and development of the parasite in the mosquito host and Sharma’s group has been involved in dissecting signalling pathways in the malaria parasite, which are relevant for infection and propagation in human erythrocytes past several years.

“Specifically, we have been working on Aurora kinases like Ark1 for almost five years,” Tewari said.Annu Nagar, a Ph.D student with Sharma’s group, investigated how Ark1 regulates division of the parasite during blood-stage development. Ryuji Yanase and Mohammed Zeeshan and others from Tewari’s group helped unravel the role of Ark1 in the vector host. “The contributions of Eelco Tromer, University of Gronegen, were critical too in the identification of the novel Ark1-CPC in the parasite using his expertise in computational biology and bioinformatics,” said Dr Sharma.These and other related studies were funded by a Team Science Grant of the Department of Biotechnology (DBT)/Welcome Trust India Alliance which facilitated the collaboration between Sharma, Prasad and Tewari groups and the European Research Council.