The zebrafish, Danio rerio, has become a popular model organism in basic biology and biomedicine. It is easy to breed in the laboratory and provides researchers with large amounts of synchronously developing embryos, making it an organism of choice for genetics and developmental biology. Embryos and larvae are largely transparent, allowing to assess organ development noninvasively. Embryos can be genetically engineered to express proteins that permit to fluorescently label distinct tissues or cell types, allow to measure neural activity, or enable visualization of hormonal signaling in the living organism. These experimental features have stimulated the use of zebrafish for research in many areas of biology, such as neurobiology, drug development, and toxicology. In this Café Scientifique presentation, Thomas Dickmeis from the Karlsruher Institute for Technology (KIT), will review some of the recent developments in the use of zebrafish embryos for the assessment of chemical compound effects on different organs and physiological processes, including developmental toxicity, cardiovascular toxicity, endocrine disruption, and neurotoxicity. A particular focus will be placed on methods for the automatization of chemical screening procedures and the sophisticated imaging possibilities available in this model system.
webinars by PrecisionTox
to be announced
FAIR data: no longer optional, but it takes a village!
19th of January 2023
Guest speakers: Prof. Susanna-Assunta Sansone & Dr. Philippe Rocca-Serra,
University of Oxford
The FAIR Principles that we have co-authored, have propelled the global debate in all disciplines on the importance of Findable, Accessible, Interoperable, and Reusable data, by humans and machines, and the need for better research data management, transparent and reproducible data worldwide. FAIR has united stakeholders world-wide behind a common concept: good data management under common standards. FAIR is a fundamental enabler for digital transformation in the public and in the private sectors. It is no longer optional. However, the FAIR Principles are aspirational, and putting FAIR into practice is work in progress; it “takes a village”!
Starting with a brief history of the Principles, Susanna will paint the landscape of key initiatives and community activities for data and software. Philippe will introduce key resources, relevant to Precision Tox, that can be used in a FAIR data/software lifecycle for a project or centre; these include ISA for describing the experimental details, and educational resources such as the FAIR Cookbook, with best practices for research data management and hands-on recipes to make and keep data FAIR.
“Broadening the use of the sentinel species
Daphnia beyond regulatory toxicology”
6th of December 2022
Guest speakers: Prof. Luisa Orsini & Dr. Xiaojing Li,
University of Birmingham
PhD student Muhammad Abdullahi, University of Birmingham & Joe Shaw, Indiana university (TBC)
“Cell-based bioassays for PrecisionTox… and what else can you do with them?”
Prof. Beate Escher
Helmholtz Centre for Environmental research
Cell-based bioassays are at the bottom of the food chain in PrecisionTox but they will hopefully provide relevant information on chemicals’ effects on the cellular level. This webinar will give an introduction to cell-based in vitro assays and how they are used for mechanistic research on cellular toxicity pathways, for the risk assessment of chemicals and in environmental monitoring & biomonitoring. A particular focus will be put on the exposure in cell-based bioassays, introducing tools on how to measure and model the exposure in high-throughput screening assays, which are performed on multi-well plates in small volumes of 20 to 100 μL. A pragmatic experimental workflow to assess stability of test compounds in bioassay media will be presented. A combination of measurements and modeling sheds further light on the exposure, which will help to interpret the results and set the detected effects in context of baseline toxicity.
“A Drosophila model for Toxicogenomics”
Prof. Robert Anholt
Prof. Trudy Mackay
Yu-Chen ‘Janet’ Pan
the Centre for Human Genetics, Clemson University
The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. The many community resources for D. melanogaster can be leveraged to identify naturally occurring variants, genes, genetic pathways and mechanisms underlying susceptibility to environmental toxins. These include the D. melanogaster Genetic Reference Panel, a population of fully sequenced and extensively annotated wild derived inbred lines, tissue- and developmental stage-specific RNA interference constructs, and mutations in most genes in the genome. We will describe these resources and show how they can be used to explore the genetic basis of sensitivity/resistance to arsenic, an ubiquitous environmental toxin of worldwide concern that presents serious health risks. We will discuss how we can identify allelic variants associated with susceptibility/resistance to arsenic and construct genetic networks associated with arsenic sensitivity. These networks can be compared with those obtained previously for susceptibility to lead and cadmium, to identify common versus specific elements for sensitivity to heavy metal toxicity. We will superimpose human orthologs on these networks as a blueprint for subsequent studies in human populations. Thus, Drosophila can serve as a translational toxicogenomics gene discovery system.
“High-throughput, alternative animal toxicity testing using the nematode Caenorhabditis elegans: An historical perspective”
Prof. Jonathan Freedman
from the University of Louisville
“Making toxicity transparent: How zebrafish embryos help evaluating adverse effects of chemicals”
Dr. Thomas Dickmeis
from the Karlsruher Institute of Technology (KIT)