It's about time: the evolution and ecology of circadian rhythms in infectious disease

Biological rhythms appear to be an elegant solution to the challenge of coordinating activities with the consequences of the Earth's daily and seasonal rotation. The genes and molecular mechanisms underpinning the clocks that drive daily rhythms are well understood. In contrast, the costs and benefits provided by daily rhythms - including how rhythms shape interactions between organisms - remain remarkably poorly understood. One of the most fundamental interactions between organisms is that between hosts and parasites. Why parasites - that exclusively live within the bodies of other organisms - exhibit biological rhythms and how their rhythms are regulated are longstanding questions with no satisfactory answers. Examining the roles of biological rhythms in disease is a new arena for studying host-parasite-vector coevolution.

The project will focus on malaria parasites, which are an excellent model system for disease-causing organisms and also of great medical and economic importance. For several centuries, the species of malaria parasite infecting a patient was diagnosed by the regularity of fever (every 1, 2, or 3 days). Fever results from the synchronous bursting of malaria parasites in the host's blood when they release their progeny to infect new red blood cells and cause the symptoms of malaria. Despite such ancient knowledge, why these parasites have a daily rhythm is unknown. However, my lab has shown that the survival and transmission of malaria parasites depends synchrony between the timing of their replication in the host's blood with the timing of the host's feeding cycles. The project will investigate why timing in related to host feeding matters for key components of parasite fitness - survival in the host and transmission to mosquito vectors.

This interdisciplinary project will break new ground by elucidating the adaptive significance (evolutionary costs and benefits) of rhythms for parasites. It will integrate a novel mix of disciplines (evolutionary ecology, chronobiology, and parasitology) and open up novel avenues for disease control. This includes the development of drugs to disrupt parasite rhythms, harnessing circadian systems to enhance immune responses, or precisely timing drug administration to make treatment more effective. Growing evidence that the daily rhythms of malaria parasites can confer tolerance to antimalarial drugs, and that the use of bed nets is changing the biting time of the mosquitoes that transmit malaria makes understanding how and why parasites exhibit daily rhythms increasingly urgent. The project will use malaria parasites of rodents (Plasmodium chabaudi) and mosquitoes.