Interplay of the metabolism and physical activity

• Applicants: Dr. Felix Loosli; Privatdozentin Dr. Claudia Muhle-Goll
• Subject Area: General Genetics and Functional Genome Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576721287

The proposed project aims to analyze the interplay between metabolism and physical activity of an organism. We want to test the hypothesis that an individual's preference for voluntary physical activity is at least partially controlled by its genetic makeup and its influence on the individual's metabolome. We will use the teleost medaka as a genetic model system for a quantitative analysis of metabolism and voluntary physical activity. In a first step, we will use an isogenic medaka reference strain (iCab) to determine how metabolism responds to changes in activity in a swim tunnel assay. Using quantitative NMR metabolite analysis, we will compare the metabolic fingerprint of key organs, namely the brain, liver and tail muscles, during normal and increased physical activity to investigate how the metabolism of key organs changes during physical activity. In a second part, we will investigate whether metabolism and voluntary physical activity correlate. To this end, we will quantify the metabolome of the inbred lines of the medaka MIKK panel using RNA seq data and NMR metabolome analysis and record their swimming behavior in a neutral activity assay. Subsequently, with the help of our cooperation partner, Prof. Birney, statistical methods will be applied to search for a possible correlation between the variance of the metabolome and the activity. The relevance of our findings will be validated using CRISPR/Cas mediated genome editing and proteomics analysis. The study we are proposing will be important for several areas of research. From a basic research perspective, it may provide new insights into the complex interactions of different complex traits in vertebrates. This will provide starting points for the search for pleiotropic effects of genetic variants in a polymorphic population. A better understanding of possible interactions of traits will also provide information on how a wild population can adapt to changing conditions, which is important with regard to climate change or the colonization of a new habitat by animals. From a biological and medical point of view, it is also of great interest to investigate which characteristics influence movement behavior. Activity patterns are closely linked to well-being and health. According to the WHO, cardiovascular disease (CVD) is the leading cause of death worldwide. Understanding the factors that regulate voluntary physical activity to prevent cardiovascular disease will therefore help to identify risk genes and improve therapies.

• DFG Programme: Research Grants