Macro-level Modeling of the Response of C. elegans Reproduction to Chronic Heat Stress

A major goal of systems biology is to understand how organism-level behavior arises from a myriad of molecular interactions. Often this involves complex sets of rules describing interactions among a large number of components. As an alternative, we have developed a simple, macro-level model to describe how chronic temperature stress affects reproduction in C. elegans. Our approach uses fundamental engineering principles, together with a limited set of experimentally derived facts, and provides quantitatively accurate predictions of performance under a range of physiologically relevant conditions. We generated detailed time-resolved experimental data to evaluate the ability of our model to describe the dynamics of C. elegans reproduction. We find considerable heterogeneity in responses of individual animals to heat stress, which can be understood as modulation of a few processes and may represent a strategy for coping with the ever-changing environment. Our experimental results and model provide quantitative insight into the breakdown of a robust biological system under stress and suggest, surprisingly, that the behavior of complex biological systems may be determined by a small number of key components. Author Summary: Dynamic response to changing conditions in the environment is an essential property of all biological systems. Whereas extensive research over the last several decades has elucidated numerous molecular responses to environmental stress, there is much less known how these translate into organismal-level responses. Two types of modeling approaches are often used to bridge this gap. Fine-grained models seek to explain phenomena as resulting from interactions of large numbers of individual components. This approach demands a highly detailed knowledge of the underlying molecular mechanisms and has an inherent difficulty in crossing spatial scales and organizational hierarchies. As an alternative, here we present a macro-level model of reproduction in C. elegans that uses fundamental engineering principles, together with a limited set of experimentally derived facts, to provide quantitatively accurate predictions of performance under a range of physiologically relevant conditions. One important finding is that individuals within a population display considerable heterogeneity in their response to heat stress. This could be a reflection of different strategies for coping with the ever-changing environment. Our study further demonstrates that dynamic behaviors of systems may be determined by a small number of key components that lead to the emergence of organismal phenomena.