Clocking in with malaria parasites

June 09, 2020

The parasites responsible for malaria seem to march to their own beat.

The mystery behind the molecular basis of how these parasites synch their rhythm in replication to the host's clock-driven rhythms has been solved. A new genetic analysis led by KAUST scientists revealed Plasmodium parasites have internal timekeeping systems that help the organism maintain essential oscillations in gene expression levels and cell cycle activities.

Just as humans reset their own biological clocks in response to light-dark cues, malaria parasites time their own rhythms to host signals to maximize their growth success.

The finding of a genetic metronome within the malaria parasite, as well as one component of this timekeeping mechanism, could open new pathways for combatting one of the world's deadliest contagious diseases. Saudi Arabia is on the verge of malaria eradication, but the disease continues to affect its southwestern border, where infections have proven difficult to treat and parasites are increasingly resistant to existing drugs.

"The knowledge from our study has the potential to inform new therapies for malaria elimination," says Amit Subudhi, a postdoctoral research fellow in Arnab Pain's group and the first author of the new report. "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."

Subudhi and Pain teamed up with colleagues from the University of Edinburgh, U.K., and from Nagasaki University, Japan, to profile gene activity patterns in mouse-infecting malaria parasites. 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 periodicity when the clocks of the parasite and mouse fell out of synchrony. Likewise ; in a lab dish, human malaria parasites cultured without timing cues also displayed some degree of daily rhythmicity in gene expression. One of these genes coded for a receptor protein called SR10, which the researchers showed acts as a cog in the parasite's intrinsic clock machinery.

Without this protein, the usual 24-hour cycle of the rodent Plasmodium parasite became shorter, leading to defects in DNA replication and other cellular processes as well as protein breakdown. According to Subudhi, SR10 likely serves as a link between host circadian rhythms and the endogenous time-keeping ability of the parasite.

The KAUST researchers plan to dissect the molecular components of the SR10-mediated signaling pathway in search of novel drug targets. "Our work does not stop here," notes Pain. "Our next aim is to understand the chemical nature of the host-derived cues that the parasite receives to adjust its life cycle and its biological clock," he says.

King Abdullah University of Science & Technology (KAUST)

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to