Severe ocular disorders are affecting the lives of more than 100Mill people world-wide and at least 25% of the population above 70 years of age, a growing demographic group in EU. More than 8 million people lose their lives to cancer every year, making cancer a leading cause of pre-mature mortality in the world. The main hallmarks of severe eye conditions (i.e angiogenesis, inflammation and vascular permeability) play also pivotal roles in cancer, being therapeutic targets to treat both kind of diseases. The overall goal of 3D-NEONET is the improvement of available treatments for cancer and ocular disease by enhancing drug discovery-development and delivery to targeted tissues, through advanced international co-operation between academic and non-academic partners. The interdisciplinary expertise provided by 18 partners in 7 countries encompasses among others: drug screens, ADME, toxicology, preclinical models, nanotechnology, biomaterials and clinical trials. After the success with ongoing FP7-IAPP project 3D-NET (Drug Discovery and Development of Novel Eye Therapeutics; (www.ucd.ie/3dnet), we are assembling 3D-NEONET, this enlarged European interdisciplinary consortium that will join forces and exchange skills to enhance current therapies in oncology and ophthalmology. The 3 global objectives of 3D-NEONET are: 1- Enhance the discovery and development of novel drugs, targets and biomarkers for ophthalmology and oncology. 2- Improve the Delivery of Therapeutics for Oncology and Ophthalmology 3- Enhancement of Research, Commercial and Clinical Trial Project Management Practices in these fields. Through participation in the program, 3D-NEONET is the vehicle for driving synergies between academic and non-academic participants leading to increased scientific and technological excellence as well as tangible innovative outputs that will strengthen the competitiveness of both the researchers and industries of the network even beyond the lifetime of the network.

A fundamental challenge for Neuroscience is to understand how neural circuits process information from the outside world and internal physiological states, to produce versatile but reliable behavior. Two major research challenges are: 1) the complexity and distributed nature of neural circuits; 2) the need for data spanning multiple scales from molecular and activity phenotypes of single cells through to circuit connectivity and population dynamics and finally the behavioral output itself. The goal of the ZENITH ETN, “ZEbrafish Neuroscience Interdisciplinary Training Hub”, is to understand how neural networks mediate perception and behavior. We will exploit the advantages of zebrafish as a small transparent vertebrate with superb genetic accessibility and use cutting-edge technology to elucidate the interactions between molecules, cells and entire networks that ultimately generate adaptive behavior. Our training goal is to create collaborative, interdisciplinary young scientists who can tackle major challenges within neuroscience research. Training in cutting-edge technologies and analytical frameworks will enable this next generation of researchers to perform integrated, multi-scale analyses to elucidate the neural basis of naturalistic behavior. Training is centered on highly collaborative projects between physicists, mathematicians and biologists that will expose ESRs to broad training with academic and industrial partners. Advanced optical methods and genome-editing will be utilized to link molecules to circuits, to map connectivity between cell types across the nervous system and to build computational models of brain activity that will be experimentally tested. Overall ZENITH will help to change the way young scientists are trained in Europe and provide the conceptual, technical and analytical skills needed to take on the challenge of understanding how the beautifully complex circuits of the vertebrate brain control behavior.

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.

The complex nature of pharmaceutical new molecules generation, both in terms of R&D process and regulatory requirements, indicates a huge need for innovative tools/services for optimal delivery to patients of novel medicines in the fastest and cheapest manner. The pharmaceutical industry strives continuously to produce new, safer and more efficacious drugs for unmet needs, evolving different synthesis techniques, expanding numbers of leads for potential drug candidates. However, this abundance has also created a new set of challenges in efficient processing of drug libraries for target validation and toxicity assessment. High-throughput screening (HTS) is thought to be key in handling this flow of new potential therapeutics in a systematic and time-efficient manner. But, there is a strong evidence that in vitro cell-based assays and subsequent preclinical in vivo studies do not yet provide sufficient pharmacological and toxicity data or reliable predictive capacity for understanding drug candidate performance in vivo. The model developed by ZeClinics with specific focus on cell and molecular interactions and physiological parameters improves this situation and helps to determine the corresponding responses to bioactive agents. The aim of ZeCardio project is to use zebrafish model to develop HTS of large libraries in live organism for cardiotoxicity assessment. Our complete system analyses the impact of drugs and diseases in heart performance (Heart rate, Arrytmia, AV Blockage and Ejection fraction) and the performance of the vascular system (Blood flow and vasodilatation/constriction).

Genome editing technologies based on CRISPR/Cas systems allow targeted genomic modification with unprecedented precision and have emerged as powerful alternatives to the conventional gene therapy approaches for various human diseases, with a series of clinical trials in progress. However, some crucial challenges remain to be addressed to enhance efficiency and safety and decrease costs of treatments. Current viral-based delivery systems are associated with high risk of toxicity and immunogenicity and remain highly expensive. We will develop a new generation of non-viral delivery systems for gene editing tools based on the use of modified nanoparticles with human-derived protein moieties that will allow targeting the tissue and cells of interest in vivo with minimal adverse effects. Prime editors have raised exciting possibilities for double-strand break free genome editing. However, a major limitation of current prime editors is highly variable efficiency both from one target to another and between cell types. We will design and evaluate novel prime editor tools in order to both increase activity per se and overcome cell-specific limitations.We will test our approach on the hematopoietic system to treat Sickle Cell Disease, avoiding the challenges and risks of hematopoietic stem cell manipulation associated with current gene therapy approaches, and thus providing a treatment much simpler, safer and cost-effective to implement. Our technological breakthroughs address two key obstacles in cell and gene therapy: gene editing efficiency and systemic delivery. The novel prime editors and targeted nanoparticles that we will engineer will be combined to make unprecedented off-the-shelf, recombinant biologics for gene therapy. The versatility of the design of these novel recombinant biologics makes them suitable for the treatment of a vast majority of genetic diseases.