Café scientifique

webinars by PrecisionTox

A Drosophila model for Toxicogenomics
Café Scientifique with
Prof. Robert Anholt
Prof. Trudy Mackay
Maria Adonay
Yu-Chen ‘Janet’ Pan
from the Centre for Human Genetics, Clemson University
chaired by Valentin Salamone, Altertox
25 January 2022 / 

3:00-4.30 pm UK time.

We are delighted to invite you to the next edition of free “café scientifique” on the 25th of January from 3:00-4:30 pm UK time on the topic of “A Drosophila model for Toxicogenomics”

Online event via Zoom
Register Online


Abstract: 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.


“Cell-based bioassays for PrecisionTox ….. and what else can you do with them?”

Café Scientifique with Prof. Beate Escher
9 November 2021 / 

3:00-4.30 pm UK time.


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.

Meet the speakerProf. Beate Escher 

Beate Escher is Head of Department of Cell Toxicology at the Helmholtz Centre for Environmental Research in Leipzig, Germany and Professor at the Eberhard Karls University Tübingen, Germany. She is also lecturer at the Swiss Federal Institute of Technology in ETHZ, Switzerland, holds an honorary professorship at the University of Queensland and an adjunct professorship at Griffith University, Australia. She was Associate Editor for Environmental Science and Technology from 2012 to 2020 and is member of the Board of Reviewing Editors at Science. In 2013 she won the Australian Water Association AWA National Research Innovation Award for her work on cell-based bioassays in water quality assessment. Escher’s research focuses on developing scientifically sound in vitro tools and methodologies for risk assessment of micropollutants in the environment and in people. Escher’s expertise includes the development of in vitro bioassays and applications of new approach methods for monitoring and mode-of-action based effect assessment of organic micropollutants including pharmaceuticals, pesticides and persistent organic pollutants, environmental transformation products, and mixtures. She works towards improving dosing and interpretation of high-throughput in vitro bioassays and developed the robotic bioassay platform CITEPro at UFZ ( More practically oriented aspects include passive sampling of sediment, biota and human tissue and effect-based methods for water quality assessment, covering a wide range of different water types from wastewater to drinking water and treatment processes including biological treatment, filtration and advanced oxidation processes, as well as applications of in vitro tools for biomonitoring in fish, mammals and human tissues

Towards Precision Toxicology


Project info

Precision Tox

Grant agreement ID : 965406

Coordinated by

The University of Birgmingham UK


Ongoing project

Funded under


Start date

01 February 2021

End date

31 January 2026

Overall budget

€ 19 305 583,75

EU contribution

€ 19 305 583,75

“PrecisionTox aims to transform regulatory toxicology by simultaneously deploying five biomedical model species and human cell lines to uncover molecular toxicity pathways shared across the animal kingdom, enabling chemicals to be classified according to their precise effects on human health.”

Scientific innovations identifying genes connected to disease have already transformed health care by delivering ‘precision medicine’. Yet it is well known that disease results not from genes alone but from the interaction between genes and the environment. Precision toxicology therefore builds toward the ultimate goal of safeguarding health by understanding how environmental factors such as pollution contribute to illness and premature death.

“We do not rely on the strength of the science alone to engineer change.”

Precision Toxicology is based on three core concepts. PhyloToxicology replaces traditional animal testing with an Evolutionarily Diverse Model Suite of organisms from multiple branches of the tree of life. Variation in Susceptibility determines safe levels of exposure to chemicals based on genetic variation. Embedded Translation engages directly with regulators and other key stakeholders in project planning, selection of chemicals for investigation, and case studies for applying Precision Toxicology in policy and law.

Phylogenetic Toxicology (Phylotoxicology)

Problem: Whole-organism toxicity testing is crucial but no single model is a perfect human surrogate.

Although mammals such as rats are considered the ‘gold standard’ for toxicology research, ample evidence demonstrates that these animals are not perfect predictors of human response to chemical exposure. Indeed, no animal is a perfect human substitute. This limitation — along with the desire to reduce expenses, improve the pace of testing, and reduce experimentation on animals — have driven recent toxicology efforts to instead use human-derived cell-lines. Unfortunately, focusing on cells has major drawbacks as toxic response often involves multiple cell and organ systems. The biological processes governing health cannot be fully observed by looking at isolated strains of cells.

Solution: Evolutionarily diverse model organisms plus human cell lines (Phylotoxicology).

Our consortium’s approach overcomes these limitations by leveraging the power of the phylogenetic tree, also known as the tree of life. All animals share the same genetic ancestry and, despite having branched off into diverse forms through evolution, animals continue to share much of the same DNA. Importantly, genes that govern disease response are among the most likely to be shared among different animals. As a result, instead of using traditional mammal models like rats, greater accuracy can be achieved by using a diverse range of biomedical model species — fruit flies, water fleas, round worms, and embryos of frogs and zebrafish — along with human cell lines to observe what happens when organisms are exposed to chemicals. Moreover, by using advanced approaches to analyzing activity at the molecular level, we can identify the fundamental biological mechanisms by which these organisms — and humans — respond to toxic chemical exposure.

Variation in Susceptibility

Problem: Exposure limits are set through guesswork.

Current methods for establishing safe exposure levels to toxic chemicals begin with quantities known to cause harm to one specific breed of mammal – usually a type of rat – and then apply some factor of 10 as a safety buffer. For example, if the presence of 5 parts per million of a chemical in water causes cancer in the specific rat strain used in the experiment, then the safe exposure level might be set at 0.05 parts per million for a human water supply (applying 102 as the ‘adjustment factor’). This guesswork not only risks putting people in harm’s way, but also might overestimate potential harm, leading to unnecessary anxiety and regulation. Additionally, this arbitrary approach fails to take into account that some people (and animals) will be more vulnerable to harm from a given toxic chemical than others due to genetic variation in susceptibility.

Solution: Study markers of susceptibility.

PrecisionTox addresses this challenge by conducting a detailed study of population variation with respect to the genes governing toxic response. Susceptibility to harm from exposure to a given chemical is a trait and, like any other trait, varies among individuals. By identifying gene sequences modulating molecular toxicity pathways, and by evaluating linkages between the genetic targets and individual susceptibility using unique genetically diverse model systems and human cell lines, informed estimates of safe exposure become possible.

Embedded Translation

Problem: Scientific answers are not sufficient; change requires buy-in from decision makers. 

Although there is broad interest in moving away from traditional animal testing, replacing old standards with new ones is a difficult task. Change often produces anxiety, and decision makers can be reluctant to promote approaches with which they are unfamiliar.

Solution: Co-produce PrecisionTox with key decision makers.

Rather than push scientific findings towards regulators and private companies at the end of the project, PrecisionTox instead works directly with a Stakeholder Advisory Group to gain insight, guidance, and feedback on producing results that can be used in the real world. This group of experienced regulators and private sector experts actively participates in shaping project activities — including selecting chemicals for testing, identifying and addressing challenges to uptake of new testing methods, participating in case studies for integrating findings into regulation, and helping to spread the word about project results.


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