Cellular stress signaling

The aim of our work is to investigate the effects of cellular stressors (e.g. particles, genotoxins and reactive oxygen species) on biological systems. We apply systems biology approaches (transcriptomics) and network analyses, to unravel underlying mechanisms of action. In particular, we focus on oxidative stress and DNA damage as triggers for stress-induced signal transduction. These processes are studied in both cell cultures and zebrafish models. To achieve this, we employ chemical and genetic perturbation strategies in order to investigate signal processing across various levels of biological organization, from individual cells to organs and entire organisms.

Current projects:

1) As part of the cross-PoF program activity ToxiDUST: Toxicity and Characterization of Health Relevant Atmospheric Fine-Dust from Emerging Sources, aerosols of different origins and compositions (including both naturally occurring and technically produced aerosols) are analyzed and evaluated with regard to their biological effects using advanced air-liquid interface exposure (ALI) systems. These projects are carried out in close collaboration with colleagues from the Institute of Technical Chemistry at KIT (https://www.itc.kit.edu/index.php). For more details, see also (https://finest-project.de/sub-projects/).

2) The ‘European Partnership for the Assessment of Risks from Chemicals’ (PARC) was developed with the overarching goal of improving knowledge about chemical substances in order to better protect human health and the environment (https://www.eu-parc.eu/). Over a seven-year period, this initiative brings together 200 organizations from across Europe. Within this framework, our group is specifically focused on investigating the mechanisms of action of non-genotoxic carcinogens.

3) As part of the EU Horizon 2020 project ‘Precision Toxicology’ (https://precisiontox.org/) we use metabolomics and transcriptomics to determine cellular responses to 200 selected chemicals (including drugs and environmental pollutants) in human cell cultures. In addition to human cell lines, he consortium utilizes a diverse range of well-established biomedical model organisms —such as fruit flies, water fleas, roundworms, and embryos of frogs and zebrafish. Artificial intelligence (AI) methods are also applied to identify molecular toxicity pathways shared across the animal kingdom. We closely collaborate with the laboratory led by Thomas Dickmeis, which conducts complementary experiments using zebrafish embryos.

4) Zebrafish embryos are exceptionally well-suited for the systematic study of teratogenic and embryotoxic effects of chemicals. Thanks to their small size, externally developing embryos, fully sequenced genome, and the availability of numerous genetic mutants, zebrafish represent one of the most promising vertebrate models for mechanistic studies in teratology, toxicology, and toxicogenomics. Because they develop outside the maternal body, adverse effects of chemical exposure can be observed from the earliest stages of development.
Unlike in vitro studies, zebrafish embryos allow the assessment of toxic effects within a complex, intact vertebrate organism. The zebrafish facility at KIT in Karlsruhe is among the largest in the world and, together with advanced high-throughput automated microscopy systems, supports efficient large-scale toxicity screening in zebrafish embryos.

In recent years, we have established the zebrafish embryo as a model organism for studying the biodistribution and clearance of nanomaterials. This is particularly relevant in the rapidly evolving field of nanomedicine, where the mechanisms governing the distribution and elimination of nanocarriers and associated drugs remain poorly understood. Inefficient targeting and unintended scavenging of nanomedicines are considered major obstacles to their further development and clinical application.
Thanks to its optical transparency and the availability of genetic tools to label specific cell types and organs, the zebrafish embryo enables high-resolution, real-time imaging of nanomaterials in vivo. This powerful system allows us to investigate both the physicochemical properties of nanomaterials and the biological processes that influence their distribution and clearance, ultimately contributing to a deeper understanding of their kinetics and modes of action.