Discovery of why timing matters to malaria parasites reveals a vulnerability that could be exploited for future treatment strategies. The discovery of a protein belonging to the parasite, known as SR10, links the parasite’s internal time-keeping ability to their host’s biological clock, a new study reveals. A new genetic analysis revealed Plasmodium parasites, that cause malaria, have internal timekeeping systems that schedule its essential cell cycle activities. Just as humans set their own biological clocks in response to light-dark cues, so too do malaria parasites. Genetic Metronome Parasites maximise their growth and survival by adapting their rhythms according to the time-of-day of their host. The finding of a genetic metronome within the malaria parasite, as well as one component of the timekeeping mechanism, could open new pathways for tackling one of the world’s deadliest diseases. Malaria, spread by mosquitoes, cause an estimated 200 million infections worldwide every year. The parasites have proven difficult to treat and are increasingly resistant to existing drugs. Researchers from the University of Edinburgh teamed up with the King Abdullah University of Science and Technology (KAUST) and Nagasaki University, Japan, to study gene activity patterns in mouse-infecting malaria parasites. Rhythmic Genes They found that more than half of all the parasite’s genes exhibited 24-hour cycles of activity, ramping up and down at regular daily intervals. This pattern is consistent with the characteristic rhythms of fevers and chills seen in people infected with malaria. Around half of the rhythmic genes lost their periodic activity when the clocks of the parasite and mouse fell out of sync, impairing important cellular processes. Human malaria parasites cultured in total darkness also displayed daily cycles of activity in gene expression. Timekeeping Mechanism One of these genes coded for the SR10 protein in both mouse and human parasites, which the researchers showed acts as a cog in the parasite’s internal clock machinery. Without this protein, the usual 24-hour cycle of the mouse Plasmodium parasite became shorter, leading to defects in DNA replication and other cellular processes. The team’s next step is to understand what information SR10 relays to the parasites about the timing of host rhythms. How and why malaria parasites replicate rhythmically in the blood are long-standing mysteries. Revealing that timing matters for essential cellular processes, and finding a component of the parasite’s time-keeping, suggests that new drug treatments could disrupt parasite timing and provides a clue for achieving this. Sarah Reece, Professor of Evolutionary ParasitologyThe University of Edinburgh The knowledge from our study has the potential to inform new therapies for malaria elimination. This information might allow doctors to formulate drug regimens in which patients take anti-malarial therapies with known target genes at particular times of the day so as to eliminate the malaria parasite more effectively. Amit Subudhi, First author, Postdoctoral research fellowKing Abdullah University of Science and Technology (KAUST) Related Links Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms, Nature Communications Sarah Reece’s Lab Publication date 18 Jun, 2020
