ASPIS Cluster solidarity with Ukraine

ASPIS Cluster solidarity with Ukraine

We would like to express our solidarity with Ukrainian toxicologists, scientists, students, and the whole Ukrainian nation. We fully condemn the unprovoked military aggression of the Russian government against Ukraine, and we join the numerous calls from around the world for a swift return to diplomatic relations and respect of International Law.

Today, our thoughts are with all the victims of this act of war – the displaced people, separated families, including Russian and Belarusian academics, journalists and citizens who protest against this illegal invasion and support fundamental human rights, regardless of the consequences.   

Our 70 academic, private and public partners want to convey their support to the Ukrainian researchers and students. ASPIS is driven by free thought and exchange of knowledge and we will continue our research collaboration with all those who defend peace and democratic values across borders.

 

ASPIS CLUSTER:

  • For PrecisionTox, Prof. John Colbourne (University of Birmingham) Grant agreement ID: 965406
  • For ONTOX, Prof. Mathieu Vinken (Vrije Universiteit Brussels) Grant agreement ID: 963845
  • For RISK-HUNT3R, Prof. Bob Van de Water (Leiden University) Grant agreement ID: 964537

Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation

Abstract

Mitochondrial perturbation is a key event in chemical-induced organ toxicities that is incompletely understood. Here, we studied how electron transport chain (ETC) complex I, II, or III (CI, CII and CIII) inhibitors affect mitochondrial functionality, stress response activation, and cell viability using a combination of high-content imaging and TempO-Seq in HepG2 hepatocyte cells. CI and CIII inhibitors perturbed mitochondrial membrane potential (MMP) and mitochondrial and cellular ATP levels in a concentration- and time-dependent fashion and, under conditions preventing a switch to glycolysis attenuated cell viability, whereas CII inhibitors had no effect. TempO-Seq analysis of changes in mRNA expression pointed to a shared cellular response to CI and CIII inhibition. First, to define specific ETC inhibition responses, a gene set responsive toward ETC inhibition (and not to genotoxic, oxidative, or endoplasmic reticulum stress) was identified using targeted TempO-Seq in HepG2. Silencing of one of these genes, NOS3, exacerbated the impact of CI and CIII inhibitors on cell viability, indicating its functional implication in cellular responses to mitochondrial stress. Then by monitoring dynamic responses to ETC inhibition using a HepG2 GFP reporter panel for different classes of stress response pathways and applying pathway and gene network analysis to TempO-Seq data, we looked for downstream cellular events of ETC inhibition and identified the amino acid response (AAR) as being triggered in HepG2 by ETC inhibition. Through in silico approaches we provide evidence indicating that a similar AAR is associated with exposure to mitochondrial toxicants in primary human hepatocytes. Altogether, we (i) unravel quantitative, time- and concentration-resolved cellular responses to mitochondrial perturbation, (ii) identify a gene set associated with adaptation to exposure to active ETC inhibitors, and (iii) show that ER stress and an AAR accompany ETC inhibition in HepG2 and primary hepatocytes.

Newsletter Issue #1 published

Newsletter Issue #1 published

The RISK-HUNT3R project has released a new document! Indeed, the first newsletter issue is now available on the public website. You can consult the document by clicking on the following link : Newsletter Issue #1 .

PhD JOB POSITION AT THE GERMAN FEDERAL INSTITUTE FOR RISK ASSESSMENT (BfR)

PhD JOB POSITION AT THE GERMAN FEDERAL INSTITUTE FOR RISK ASSESSMENT (BfR)

A new postdoctoral position has opened at the German Federal Institute for Risk Assessment (BfR). The available position is in the department Safety of Pesticides of the BfR and especially in the unit “Testing and Assessment Strategies. The activities includes:  modeling of Adverse Outcome Pathways (AOP) in silico, bioinformatic preparation and statistical analysis of omics data, contributing to the development of regulatory concepts for ab initio testing using in silico based NAMs, and also the publication of the acquired results.

The unit is looking for a person with a degree preferably in bioinformatics, chemoinformatics, computer science or a comparable discipline who has experience with modeling omics data is an advantage in the field of toxicology. You can access the entire job description as well as the application platform by clicking on the following link: Ph.D. job position in BfR full description.

Applications are open until March 2nd.

POSTDOCTORAL POSITION OPENED AT LUND UNIVERSITY

POSTDOCTORAL POSITION OPENED AT LUND UNIVERSITY

A new postdoctoral position has opened at Lund University, Sweden. The position is in the field of Uncertainty Analysis in Scientific Assessment, with a specific focus on NAMs and AOPs used for chemical safety assessment.

The research group is looking for a person with a degree preferably in mathematics or statistics, with knowledge about Bayesian inference, and a person who is interested in the possibility of measuring uncertainty with probability. Please feel free to share this information with people who could potentially be what the research project needs.

Applications are open until December 20th.

To apply, here is the link towards the application webpage.

PHD POSITION OPEN IN CELLULAR METABOLOMICS IN TOXICOLOGY

Our project partner Vrije Universiteit Amsterdam is recruiting a PhD student with strong background on metabolism and metabolomics.

Please check the detailed offer here: https://workingat.vu.nl/ad/phd-position-in-cellular-metabolomics/o8qucu