Rhythms of Resistance: Unraveling the impact of natural circadian variation on immunity

Washington University, Saint Louis MO

Investigators

Abstract

Project summary The research program in our laboratory is centered on understanding how immunity and defense are optimized. Using plants as model systems, we focus on how defense processes are regulated by dynamic factors such as tissue type, development, ontogeny and importantly, the interplay between circadian rhythms and immune responses. In this research program, we aim to unravel how natural variations in circadian rhythms—referred to as chronotypes—influence the timing and effectiveness of immune responses against a range of pathogens. This proposal will exploit the natural variability in the genus Solanum to rapidly advance our understanding of how circadian defense mechanisms have evolved as a function of different local environments. Our work is built on the premise that, much like in humans, the circadian clock in plants is a crucial regulator of immune function. Solanum species offer a rich diversity in circadian traits that remain largely unexplored. Research from our lab shows that the timing of immune optimization in Solanum differs from that of the classic model plant Arabidopsis, suggesting that alternate regulatory mechanisms have evolved for this important trait. These findings indicate that Solanum species have developed unique circadian adaptations to their environments, optimizing their immune responses according to their specific chronotypes and environmental cues. This diversity provides a valuable opportunity to deepen our understanding of how various environmental factors, such as light, temperature, and humidity, influence biological rhythms and circadian mediated immunity. Our laboratory will leverage the genetic and phenotypic diversity within Solanum to develop a powerful system to study these interactions and to identify key genetic variants and regulatory networks that govern circadian-mediated immune responses. Using a multimethod approach, including genome-wide association studies (GWAS), CRISPR gene editing, transcriptomics, and epigenomics, we will elucidate the genetic and molecular mechanisms underlying these processes. We will explore how these genetic differences translate into variations in disease resistance, uncovering fundamental principles of how biological rhythms modulate immunity. More importantly, the findings from our studies will advance our understanding of the mechanisms by which circadian rhythms regulate immune function, offering potential parallels to similar processes in humans. By shedding light on how timing influences immune responses across different organisms, our work has significant implications for optimizing immune-related treatments, improving vaccine efficacy, and understanding disease susceptibility in humans.