2022 Early Career Award for Biological Physics: Organization and encoding of memory in evolving environments

Biological systems, ranging from the brain to the immune system, store memory of molecular interactions to efficiently recognize and respond to stimuli. However, the strategies to encode memory can vary largely across different systems. In this talk, I will discuss how statistics and dynamics of stimuli should determine the optimal memory encoding strategies in biological networks. In particular, I will contrast the compartmentalized memory in the adaptive immune system, which primarily interacts with evolving pathogens, with the distributed memory in the olfactory cortex, which interacts with relatively static odor molecules. Focusing on the adaptive immune system, I will discuss how memory encoding could be understood in light of host-pathogen coevolution. Specifically, I will show that to achieve a long-term benefit for the host, immune memory should be actively regulated, with a preference for cross-reactive receptors with a moderate affinity against pathogens as opposed to high affinity receptors. Our theory also predicts that an organism’s life-expectancy should strongly impact the cross-reactivity of its immune memory, and we expect organisms with shorter life expectancy to carry more cross-reactive memory. This theoretical prediction can guide more comprehensive cross-species comparisons of immune systems, which is currently missing from immunological studies.