Molecular Toxicology Group

mTox Group

The Mechanistic Toxicology Group (mTOX) is dedicated to understanding how chemical exposure disrupts biology. Our main areas of research include the development of New Approach Methods (NAMs) for Developmental and Adult Neurotoxicity Testing (DNT and ANT), integration of multiple, zebrafish-based endpoints to predict toxicity outcomes, the use of molecular approaches to reveal causal mechanisms by which chemical exposure affects neurodevelopment, the investigation of chemical-microbiome interactions that influence host health, and NAM development to assess the effect of chemical mixtures on behavior and enteric nervous system development.


Build Developmental Neurotoxicity (DNT) and Adult Neurotoxicity (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, ~16% 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. mTox 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 the Partnership for the Assessment of Risk from Chemicals (PARC)  and UFZ CITE. In the PANDORA project, funded by the European Food Safety Authority, we are modifying our behavior battery, coupled with high-content imaging of transgenic zebrafish labeling dopaminergic cells, to understand how dopaminergic cell loss is linked to behavioral manifestations observed upon exposure to reference chemicals and pesticides used in Europe.

Graph 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.


mTox DNT and ANT NAM Team: David Leuthold, Nadia Herold, Renee Owen, Jana Raab, Julia Spath, Stefan Scholz, Tamara Tal

Discover 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. mTox seeks to causally describe chemical mode of action to generate regulatory confidence that a chemical pollutant is likely to disrupt neurodevelopment across taxa, including humans. Funded by the Partnership for the Assessment of Risk from Chemicals (PARC) and UFZ CITE.

Zebrafish 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.


mTox Mechanism Team: Sebastian Gutsfeld, Nicole Schweiger, David Leuthold, Renee Owen, Stefan Scholz, Tamara Tal

Integration of high-content imaging and automated behavior analysis in zebrafish embryo assays to understand and predict the effects of chemicals

Changes in embryonic development and behavior endpoints represent common endpoints in zebrafish embryo assays. However, their analysis is not fully explored due to the lack of procedures for automated and unbiased assessment of changes provoked by chemicals. Therefore, we have developed routines based on model training, imaging and video frame subtractions to establish a detailed and reproducible assessment of morphological, functional and behavioural phenotypes. Supported by own open-source software developments such as FishInspector or EmbryoMotion we apply the high-content effect assessment for the prediction of human (developmental) or environmental toxicity and to diagnose mode of actions based on effect patterns. A central aspect of our analysis is a critical analysis of specificity of the effects, by comparison to predicted, hydrophobicity-driven baseline toxicity. Furthermore, in order to understand the role of toxicokinetics for the manifestation of effects we collaborate with the department of Environmental Analytical Chemistry and Cell Toxicology for internal exposure assessment.

high content imaging Figure: Automated imaging in combination with image annotation is used for a quantitative assessment of phenotypes in in zebrafish embryos exposed to chemicals.


mTox zebrafish high content team/people: Muhammad Arslan Aslam, Ann-Kathrin Kolbitz (Alumni from Jan 2025), Vanessa Saalmann, Bingxu Chen (from Jan 2025), Gloria Chidibiere Ajugwo, Emmanuel Chukwu

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. mTox 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 Neuro-Xeno-Microbiome and UFZ CITE MibiTox Consortium.

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


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

Large scale data

mTox generates a vast amount of automated bright field and fluorescence imaging data, automated behavior datas, and underlying videos. We are working towards making our data Findable, Accessible, Interoperable, and Reusable (FAIR). We apply and integrate open source computational tools for reproducible effect assessment such as R or Python for our workflows in GALAXY KNIME or SHINY. Our imaging and effect data are archived in databases such as OMERO or INTOB. Our software tools are made available publicly via gitlab or github repositories.


mTox Data Team: Sebastian Gutsfeld, Elena Nicolay, Stefan Scholz, Tamara Tal

Effects of endocrine disrupting chemicals (EDCs) on intestinal inflammation and enteric nervous system development

To bridge chemical exposure and behavior effects, another interest of the group is to develop high-content imaging approaches to quantify cellular and sub-cellular effects of chemicals and mixtures. In the ENDOMIX project, a combination of transgenic zebrafish lines is used to understand how commonly co-occurring EDC chemicals might cause inflammation of the intestinal tract and/or alter enteric nervous system development. Funded by ENDOMIX.

five day zebrafish Figure: The maximum projection shows a five-day-old double-transgenic zebrafish larva (Tg(neurod:GFP) x Tg(mpeg1:mCherry)). Neurons, including the ones located in the intestine, are labelled in yellow (neurod), and macrophages in magenta (mpeg1), modelling their interplay under environmental chemical exposure.


EDC Team: Elena Nicolay, Tamara Tal


mTOX Group Leader

Tamara Tal Prof. Dr. Tamara Tal leads the Mechanistic 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 leads New Approach Method development for developmental and adult neurotoxicity endpoints in the European Partnership for the Assessment of Risks from Chemicals (PARC) and participates in the PANDORA and ENDOMIX consortia.


mTox Group members

mtox group

Team members

Lead

Prof. Dr. Tamara Tal
Senior scientist
2019 - present
Email

Dr Stefan Scholz
Senior scientist
2002 - present
Email

Dr David Leuthold
Postdoctoral scientist
2019 - present
Email

Nicole Schweiger
Technician
2019 - present
Email

Sebastian Gutsfeld
PhD Student
2020 - present
E-Mail

Nadia Herold
PhD Student
2022 - present
E-Mail

Camila Zanini
Researcher
2022 - present
E-Mail

Chloe Wray
PhD student
July 2023 - present
Email
Julia Spath
Master Student
2023 - present
Email
Renee Owen
PhD student
2023 - present

Email

Drayce Adams
student researcher
2024 - present
Email
Elena Nicolay
PhD student
2024 - present

Email

Siraz Kader
student researcher
2024 - present

Email

Emmanuel Ogwu Chukwu
PhD student
2024 - present

Email

Gloria Chidiebere Ajugwo
PhD student
2024 - present

Email

Jana Raab
Student researcher
2024 - present

Email

Alumni

Julia Nöth, Doctoral student 2020-2022. Next Position: Heraeus, DE.

Gabriel de Macedo, DAAD Visiting PhD Fellow, October 2022 - February 2023.

Ifeoluwa Omoyeni, Erasmus Master’s Student, February-July 2022. Next position: Associate Toxicologist, Broughton Life Sciences, UK

Dr. Luísa Becker Bertotto, US EPA ORISE Postdoctoral Fellow, 2018-2019. Next position: Postdoctoral Fellow, Scripps Research Institute.

Shaza Gaballah, US EPA ORISE Post-Baccalaureate Trainee, 2017-2019. Next position: PhD student at Duke University, Stapleton Lab.

Allison Kvasnicka, US EPA Undergraduate Research Volunteer (Summer 2017) and ORISE trainee (Summer 2018). Next position: Research Specialist, BioAgilytix.

Dr. Tara Catron, US EPA ORISE Postdoctoral Fellow. Next position: Ecotoxicologist, BASF.

Drake Phelps, US EPA ORISE Post-Baccalaureate Trainee, 2016-2017. Next position: PhD Student NCSU Neuroimmunology Program, Yoder Lab.
 

Publications 

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2025 (2)

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2024 (9)

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2023 (12)

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2022 (12)

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2021 (13)

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2020 (10)

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2019 (8)

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2018 (9)

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2017 (4)

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2016 (6)

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2015 (8)

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