15 early stage researchers (ESRs), from 11 different countries, were recruited and relocated to the 13 European host institutes. ESR training was focused to chemical safety testing and in vitro and in silico methodologies. Within their own specific project ESRs maintained a high level of collaboration to the other projects. This was particularly evident in the project-wide transcriptomic experiment, which was designed and executed by all ESRs generating 2880 samples with 3565 expressions levels per sample. The work was an in3 community effort at all stages including design, sample preparation, quality control, storage, shipment, tracking, meta-tagging and data analysis. A transcriptomic data analysis workshop (the final face to face meeting before COVID restrictions) took place in Ljubljana in February 2020 to facilitate the bioinformatic approaches.
The COVID-19 pandemic prevented travel within the in3 network from March 2020 onwards, which impacted on planned in3 face to face meetings, scheduled scientific conferences (international conferences were cancelled in 2020), and secondments. Despite these disruptions and facilitated with a 6 month project extension, the scientific and training goals were reached and even surpassed expectations. The rapid adoption to online dissemination tools likely also increased the projects penetration.
The core scientific achievements of the in3 project were:
• Extensive training on a theoretical and practical level in interdisciplinary aspects of computational and experimental toxicology to all in3 ESRs
• Development of 10 optimised protocols for the differentiation of human iPSC into brain (brain spheres and neuronal cells), lung (epithelium), liver (hepatocyte-like cells), kidney (podocyte-like and proximal tubular like), immune (alveolar macrophage like cells, monocyte like cells) and vascular endothelial cells (visceral and blood-brain barrier like)
• Characterisation and cross comparison of these models on a transcriptome level with and without exposure (2880 samples transcriptomic profiles were generated with the 10 model systems, 10 core compounds and 188 extension compounds).
• Examination and delineation of tissue specific effects of compound exposures (e.g. paraquat)
• Application of pharmaco/toxicokinetic modelling
• Advances in human p-glycoprotein (ABCB1) modelling approaches
• Further development of adverse outcome pathways and quantitative adverse outcome pathways (qAOPs)
• Further development and optimisation of QSAR and read-across tools
The project activities and results were well disseminated through social media (twitter, linkedin, youtube), scientific conferences, out-reach activities (e.g. to schools) and scientific peer-reviewed publications(18 to-date). In3 was represented at a total of 82 events with 84 oral communications and 41 poster presentations with 10 ESR awards. Dissemination highlights included dedicated in3 sessions at the European Society of Toxicology (ESTIV) conference Berlin, October 2018, where all 15 ESRs gave a flash presentation, the online in3 project meeting December 2020, where the presentations are available online, participation in the Science is Wonderful 2019 MSCA activity, the PYMCON 2020 meeting and presentation at House of Commons of the UK parliament for STEM 2020. An in3 inspired company called in3 solutions has also been set up by one ESR.
