All chemicals whether they are drugs, cosmetics, agrochemicals or others need to be tested for their safety to man and the environment. The use of whole animal studies for the prediction of adverse effects in man, is problematic due to species dependent effects, high costs and a large burden to animals in terms of numbers and suffering. While there have been major improvements in human in vitro and in silico techniques, there is still a lack of an integrated risk assessment platform. The in3 proposal aims to significantly further the development of animal-free chemical and nanomaterial (NM) safety evaluation by creating a scientific and training program aimed at integrating human in vitro testing with computational approaches. The project will focus on human induced pluripotent stem cells (hiPSC) derived tissues, including liver, kidney, brain, lung and vasculature and to utilise mechanistic toxicology, quantitative adverse outcome pathways, biokinetics, cheminformatics and modelling approaches to derive testable prediction models. hiPSC present the major advantages provide non-cancerous derived tissues with identical genetic backgrounds. All Early Stage Researchers (ESRs) will work towards the same goal, utilising the same chemicals, donor cells, assays and software packages. All data will be centrally housed in standardised formats, appropriately annotated and linked with protocols and material information. While ESRs will hone their skills in their own field of expertise, they will also collaborate to create an in depth safety evaluation testing platform for the chosen test compounds. By interaction, problem solving, training and secondments over the three years, they will acquire a unique set of interdisciplinary skills for chemical and NM safety assessment. The project aims to accelerate the realisation of animal-free safety assessment and to graduate 15 PhD students with the ideal skill sets to carry out the strategy designed in in3 in the near future.

StarT will create an interdisciplinary and intersectorial European training network focusing on different aspects of autosomal recessive Stargardt disease (STGD1), a frequent inherited blinding disorder that affects an estimated 925,000 persons worldwide. StarT research aims to uncover the regulation of its disease gene ABCA4 and its missing heritability, in order to develop novel treatments. StarT training will give young researchers unparalleled training opportunities in outstanding vision research groups with unique expertise in omics technologies, bio-informatics, stem cell biology, animal models of disease, and therapeutics, providing each ESR with the necessary competences in state-of-the-art academic and industrial research. STGD1 is due to ABCA4 mutations, however up to 35% of STGD1 cases carries one or no ABCA4 coding mutation. New unconventional classes of ABCA4 mutations were recently discovered by us, the significance of which largely remains elusive. In order to understand the mechanisms triggered by these missing ABCA4 mutations and to design new therapies for STGD1 cases, challenging research questions will be addressed by the integration of unique skills from this network. Early-Stage Researchers will perform cutting edge research using innovative and interdisciplinary approaches: (functional) genomics and transcriptomics, bio-informatics, CRISPR/Cas9 genome editing, generation of stem cell and animal disease models and design of new treatments. The training objectives will be met through academic and industrial training-by-research via individual research projects, secondments, and network-wide training sessions.

SCilS will create a multidisciplinary and intersectoral European training network focusing on ciliary signalling in development and disease. Primary cilia are microtubule-based cell surface projections that have evolved to be key signalling hubs of our cells, as they concentrate or segregate components of major cellular signalling pathways. Control of ciliary signaling output requires a high degree of regulation and critical feedback, which is needed for robustness in development and cellular homeostasis of different tissues and organs. Dysfunctional cilia can therefore lead to >35 severe human genetic traits (ciliopathies) with highly heterogeneous, overlapping phenotypes. Ciliopathies affect as many as 1 in 400 people, and for the majority of cases efficient therapeutic interventions are currently unavailable. SCilS research aims to uncover the multi-level organization and regulation of cilia-mediated signalling pathways in order to understand ciliopathy disease etiology and identify novel therapeutic targets. This challenging task will be accomplished by integrating unique expertise and cutting edge technology available within the SCilS network, including structural biology, super resolution imaging and cryo-electron tomography, state-of-the-art genomics, proteomics and bioinformatics, (stem) cell biology and biochemistry, as well as organoid technology and zebrafish models. SCilS training will give Early Stage Researchers (ESRs) unparalleled training opportunities in outstanding academic and industrial settings through training-by-research via individual research projects, secondments, and network-wide training sessions. All individual training and research activities have been designed to provide each ESR with the necessary broad competences in state‐of‐the art academic and industrial research. The network will thereby make a career in both industry and academia attractive to the ESRs and improve their career prospects in both private and public sectors.