The evolutionary origin of nutrient homeostasis in animals

Animals can only live, grow and move if their cells are constantly supplied with nutrients. For that reason, every animal needs to ingest food and distribute the nutrients to all cells of the organism. Some animals, such as vertebrates or insects, are able to store nutrients in certain body parts and release them again if required. In that way, they can keep a stable nutrient balance. This capacity, also termed nutrient homeostasis, is accomplished by a complex organ system that coordinates the nutritional needs of the body with the uptake or release of nutrients. In vertebrates, for example, food ingestion triggers the release of brain hormones leading to Insulin secretion from the pancreas into the blood. High Insulin blood levels then promote global glucose uptake and fat synthesis. Insects, in contrast, do not possess a pancreas but control global nutrient levels mainly by secreting Insulin-like peptides (ILPs) from brain neurons. Much simpler animals such as sponges lack nutrient storing capacities and therefore rely almost entirely on a constant nutrient supply from the environment. So far, it is completely unknown how nutrient homeostasis emerged during animal evolution. We aim to understand the evolution of this fundamental system by studying cnidarians such as sea anemones or jellyfish. These animals exhibit a simple, easily accessible body plan. They lack organs, a brain or a blood circuit and consist of only two cell layers. Nevertheless, they possess Insulin- like peptides (ILPs) and the ability to store food. We plan to study the interplay between ILP-secreting cells and nutrient storage cells in the sea anemone Nematostella vectensis. In particular, we are interested in the connection between ILP production and food availability, and the role of ILPs in the storage and release of glucose, fats and proteins. This study will help understanding the function and evolution of the Insulin system and might unveil the evolutionary origin of the vertebrate pancreas. A second part of the project is based on the observation that the gonads of sea anemones and jellyfishes act as nutrient storage organs. If this function is ancient for all cnidarians, we expect similar genes to control the uptake or release of nutrients into the gonads of different cnidarians. We therefore plan to detect all actively transcribed genes under feeding or fasting conditions in the gonads of the sea anemone Nematostella vectensis, the moon jelly Aurelia aurita, and the jellyfish Clytia hemisphaerica. A comparison of these datasets will unveil gene products that were essential during the evolution of nutrient homeostasis.

In bilaterian animals (such as flies, nematodes or humans), Insulin/Tor signalling is an important molecular pathway to control nutrient uptake, metabolism and growth rates. The main goal of the project was to study how these fundamental physiological properties have emerged during animal evolution. We have therefore studied if the Insulin/Tor signalling pathway underlies similar processes also in cnidarians, the sister group of bilaterian animals. The project has provided first insights into the cellular and molecular changes occuring during fasting of sea anemones. We have shown that the activity of some Insulin-like genes change during fasting, and that the inhibition of the Insulin/Tor pathway leads to decreased growth rates. These results suggest that the Insulin/Tor pathway controls body growth, as previously described for bilaterians. These first insights confirmed our initial hypothesis, and have encouraged us to continue studying the function of the Insulin receptor by generating mutants. The second part of the project had the goal to identify new genes that regulate nutrient-depending growth processes in sea anemones. With that aim, we have studied the global changes in the transcriptional levels of genes active in nutrient-storing and insulin- secreting tissues. Interestingly, we found that genes involved in cell division, and in the development of neurons and stinging cells are among the strongest affected. Altogether, these data have build the foundation for further studies to understand how nutrition affects and regulates cell proliferation, a process also playing a major role during tumor formation and growth, using the sea anemone as model organism.