Developmental Biology/ Physiology

Individual variation is the critical parameter in the interplay of the organism with its environment that results in states of health or disease as well as in environmental homeostasis. It must be understood to translate findings from laboratory models to real world scenarios and ultimately to the human context. The central issue is to distinguish between determined phenotypes, those influenced by individual variation, and stochastic events. A significant barrier in achieving this is the deliberate selection of inbred genetic models to reduce variation as a source of noise and ensure experimental reproducibility. We tackle these issues using the unique properties of medaka fish, which can be fully inbred from the wild, in contrast to most other models. We are representing a natural population by a panel of inbred lines derived from it and have already established a panel of 111 diverse medaka lines (all entirely sequenced) originating from a single natural population. In-depth phenotyping of these lines at scales ranging from organismal to molecular phenotypes, using methods that can be highly replicated will allow establishing the underlying complex genetic contributions. We selected a number of the phenotypes for investigation in entirely wild fish from the same source population. State-of the-art analytical methods will distinguish between genetic, environmental, and stochastic sources of variation and to study their interactions in the development of phenotypes. A particular focus will be to integrate this information across the cardiovascular systems of vertebrates, especially the wide range of phenotypes observed in humans. Genetic crosses combined with CRISPRCas9 techniques will determine specific causal interactions. Our study focuses on comprehensiveness and replicability to broach the essential question of distinguishing between genetic, individual and environmental effects in the stratification of phenotypes related to human disease as we move into an era of personalized medicine.