Punctual parasites: why is rhythmic replication advantageous for malaria parasites?

Year of award: 2023

Grantholders

  • Prof Sarah Reece

    University of Edinburgh, United Kingdom

Project summary

Life in a rhythmic world dictates the timing of activities for many organisms, including parasites who are confronted with myriad circadian rhythms of hosts and vectors. The within-host/vector environment changes dramatically over 24h, offering parasites rhythmic opportunities to exploit and presenting rhythmic dangers to evade. Malaria (Plasmodium) parasites are famously rhythmic; they undergo synchronous replication in the blood at particular times of day. Explaining why Plasmodium has evolved rhythmic replication is important because parasite rhythms underpin the severity and spread of infections. Our hypothesis is that Plasmodium has evolved rhythmic replication to exploit opportunities offered by the metabolic rhythms of vertebrate hosts and to maximise infectivity to mosquito vectors. Understanding, predicting, and potentially exploiting, parasite evolution requires examining parasite rhythms in the context of their entire lifecycle and integrating evolutionary ecology, parasitology, and chronobiology - an approach we have pioneered. Explaining what makes parasites successful and where their vulnerabilities lie may uncover targets for drugs and inform how to reduce transmission in manners that are robust to parasite evolution. This includes how to prevent Plasmodium's ability to tolerate antimalarials by pausing/lengthening the replication rhythm, and how to mitigate against shifts in the biting time-of-day of mosquitoes to evade insecticide-treated bednets.