Molecular Toxicology Group

The Molecular Toxicology Group (mTOX) is dedicated to understanding how chemical exposure disrupts biology. Our three main areas of research include the development of New Approach Methods (NAMs) for Developmental and Acute Neurotoxicity Testing (DNT and ANT), the use of molecular approaches to reveal causal mechanisms by which chemical exposure affects neurodevelopment, and the investigation of chemical-microbiome interactions that influence host health.

Build DNT and ANT NAMs

The developing nervous system is particularly sensitive to chemical exposure and there is heightened public concern linking the rise in children’s neurodevelopmental impairments, including learning disabilities, to environmental chemicals. From an ecological perspective, ~13% of chemicals detected in multiple EU water sampling studies have neurotoxic modes of action. Despite the link between chemical exposure and adverse neurodevelopmental outcomes, from among an estimated 350.000 chemicals in commerce, data from less than 200 OECD rodent neurotoxicity tests are available. To solve the gap in testing, we need to radically change the way we assess the potential for chemicals to harm the developing nervous system. Cellular assays fail to recapitulate complex neurodevelopmental endpoints captured in OECD rodent tests including behavior, learning, and memory. Our team builds, evaluates, and validates zebrafish embryo-based NAMs for complex behavioral endpoints including non-associative habituation learning and memory retention, and build fingerprinting systems to reveal putative chemical mode of action information. Funded by UFZ CITE.

Figure: We developed a novel zebrafish embryo behavior assay battery for the identification of neurotoxic chemicals. The battery is comprised of sequential behavior assays that quantify visual and acoustic startle responses (VSRs, ASRs), visual motor responses (VMRs), acoustic startle habituation (ASH), potentiation of habituation, and memory retention of acoustic stimuli. We use the assay to identify chemicals that disrupt complex behaviors in early life stage zebrafish.

NAM Team: David Leuthold, Nadia Herold, Tamara Tal

Delineate chemical mode of action

Zebrafish embryo behavior data has yet to be used for human and ecological risk assessment. One reason is a lack of confidence that chemical-dependent changes in zebrafish behavior represent developmentally or acutely neurotoxic endpoints that are translationally relevant. One strategy that can build confidence in the use of these data is a better understanding of underlying mechanisms that drive behavior effects. Our team seeks to causally describe chemical mode of action to generate regulatory confidence that a chemical pollutant is likely to disrupt neurodevelopment across taxa, including in humans. Funded by UFZ CITE.

Figure: CRISPR/Cas9-based gene editing of the tyrosinase gene caused significant reductions in pigmentation (light blue=uninjected control; blue=negative control crispant; red=tyrosinase crispant). This strategy is applied to test whether genes and pathways are required for chemical-dependent effects on behavior.

 Mechanism Team: Sebastian Gutsfeld, Nicole Schweiger, David Leuthold, Gabriel de Macedo, Tamara Tal

Understand chemical-microbiome interactions that affect host health

The intestinal microbiome harbors the capacity to influence the toxicokinetics and toxicodynamics of xenobiotic exposures. It is widely understood that exposure to exogenous chemicals disrupts the community structure of host-associated microbes and several reports show that chemical-selected microbiomes biotransform environmental chemicals. A major knowledge gap relates to whether xenobiotic-induced effects on microbial ecology and biotransformation causally alter the toxicity of environmental chemicals to the host organism. Until this question is answered, the microbiome will not be considered in risk assessment strategies. Our team moves the science forward to illuminate the mode of action in microbiome-mediated toxicity using the three-colonization cohort system comprised of axenic (i.e., microbe-free), conventionalized, and conventionally colonized zebrafish. Funded by Helmholtz Association W2 Award to T. Tal and UFZ CITE MibiTox Consortium.

Figure: This image depicts an axenic zebrafish larva mono-associated with a fluorescently labeled strain of bacteria.

Microbiome Team: Sebastian Gutsfeld, Nicole Schweiger, Tamara Tal, Chloe Wray

mTOX Group Leader

Prof. Dr. Tamara Tal leads the Molecular Toxicology Group at the Helmholtz Centre for Environmental Research – UFZ. She also holds a Professorship in Integrated Systems Toxicology in the Medical Faculty at University Leipzig. Prior to joining the UFZ in 2019, Tamara was a Principal Investigator at the United States Environmental Protection Agency in the Office of Research and Development. Tamara completed postdoctoral fellowships in the labs of Dr. Robyn Tanguay (Oregon State University) and Dr. Stephanie Padilla (EPA) and earned a doctorate in toxicology from the University of North Carolina at Chapel Hill under the mentorship of Dr. James Samet. Tamara co-leads New Approach Method development for developmental and acute neurotoxicity endpoints in the European Partnership for the Assessment of Risks from Chemicals (PARC), is a member of the US National Toxicology Program Scientific Advisory Committee on Alternative Toxicological Methods (SACATM), and serves as President of the Society of Toxicology (SOT) Molecular and Systems Biology Specialty Section.

mTox Group members

Team members