Time to start taking time seriously: How to investigate unexpected biological rhythms within infectious disease research

The discovery of rhythmicity in host and pathogen activities dates back to the Hippocratic era, but the causes and consequences of these biological rhythms have remained poorly understood. Rhythms in infection phenotypes or traits are observed across taxonomically diverse hosts and pathogens, suggesting general evolutionary principles. Understanding these principles may enable rhythms to be leveraged in manners that improve drug and vaccine efficacy or disrupt pathogen timekeeping to reduce virulence and transmission. Explaining and exploiting rhythms in infections requires an integrative and multidisciplinary approach, which is a hallmark of research within chronobiology. Many researchers are welcomed into chronobiology from other fields after observing an unexpected rhythm or time-of-day effect in their data. Such findings can launch a rich new research topic, but engaging with the concepts, approaches, and dogma, in a new discipline can be daunting. Fortunately, chronobiology has well-developed frameworks for interrogating rhythms that can be readily applied in novel contexts. Here, we provide a “how to” guide for exploring unexpected daily rhythms in infectious disease research. We outline how to establish: if the rhythm is circadian, to what extent the host and pathogen are responsible, the relevance for host-pathogen interactions, and how to explore therapeutic potential.