Zebrafish Endocrinology and Metabolism

Research interest

The Dickmeis laboratory explores the zebrafish as a model organism to study the interplay between hormonal signaling and metabolism in development and disease. A main focus is placed on the temporal dynamics of metabolism and endocrine regulation.

To this end, we develop biosensors to measure hormonal and metabolic signaling activity in the living animal, targeting e.g. glucocorticoid hormones, glucose or reactive oxygen species. We also employ systems biology approaches (transcriptomics, proteomics, metabolomics) to understand the temporal dynamics of metabolism and their regulation by endocrine and metabolic signaling, both during development and regeneration and across the day-night cycle. In chemical in vivo screens with zebrafish embryos, we apply tools and concepts derived from our studies to evaluate toxicity of chemicals and to identify novel lead compounds for drug development.

Below are highlighted three current projects: 

The aim of the EU funded international PrecisionTox project is to better protect the health of people and the environment by establishing New Approach Methodologies (NAMs) for chemical safety testing using a mix of genomics, metabolomics, evolutionary theory, quantitative genetics, data science, toxicology, and law. The consortium uses human cell lines and a diverse suite of well-established biomedical model organisms — fruit flies, water fleas, round worms, and embryos of frogs and zebrafish — as well as artificial intelligence (AI) approaches to uncover molecular toxicity pathways shared across the animal kingdom. 

 

Part of a heatmap depicting clustered toxicity data across five model species (the worm Caenorhabditis elegans, the fly Drosophila melanogaster, the waterflea Daphnia magna, zebrafish Danio rerio embryos, South African clawed frog Xenopus laevis embryos) and a human cell line. Chemicals can be grouped according to structural features by their toxicity profiles across the test models.

Within this project, we contribute our expertise on zebrafish embryos and examine chemical compounds specifically for their metabolic and endocrine disrupting activities. In vivo assays targeting metabolic regulation and hormonal signaling anchor the information obtained from OMICS data generated by the consortium to specific compound-induced phenotypes, generating mechanistic knowledge that can be used to better understand, predict and treat toxic compound effects. We closely collaborate with the group led by Carsten Weiss, which covers the human cell culture part of the project.

A second EU funded project, Toxbox, aims to develop a flexible, all-in-one platform for comprehensive chemical toxicity testing, which also provides advanced data integration and reliable computer models for better risk assessment. This platform will include a zebrafish module which allows to record biochemical, microscopic and behavioural readouts from zebrafish embryos treated with chemicals. We collaborate with Ralf Mikut’s group at IAI/KIT, also a partner in this consortium, to develop machine learning approaches for data evaluation from zebrafish embryo assays.

Role of reactive oxygen species (ROS) in brain regeneration
Section across the zebrafish adult forebrain expressing a transgenic hydrogen peroxide sensor. The hemisphere showing increased oxidation was lesioned and will fully regenerate within a few weeks.

In contrast to mammals including humans, zebrafish have the remarkable capability to regenerate damaged neuronal tissue within a few weeks. In our project, we apply molecular tools to visualize metabolites and ROS during the process of brain regeneration after physical injury. In this way, we hope to obtain insight into potential functions of altered metabolism and redox states during the injury response and subsequent regenerative processes.