Understanding the Rules of Life (URoL): Predicting Phenotype is one of NSF’s 10 Big Ideas and is focused on predicting the set of observable characteristics (phenotype) from the genetic makeup of the individual and the nature of its environment. The development of new research tools has revolutionized our ability to manipulate and investigate the genome and to measure multiple aspects of biological, physical, and social environments. The opportunity now is to assimilate this new information into causal, mechanistic, and/or predictive relationships among the genomic and epigenetic makeup, the environmental experience, and the phenotypic characteristics of biological systems. These relationships are the basis for the Rules of Life – the theoretical constructs that explain and predict the characteristics of living systems, from molecular and sub-cellular components, to cells, whole organisms, communities and biomes. Successful projects of the URoL:Epigenetics Program are expected to use complementary, interdisciplinary approaches to investigate how epigenetic phenomena lead to emergent properties that explain the fundamental behavior of living systems. Full proposal deadline: February 6, 2020.