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H2020Doctoral network2019–2024

NEUcrest · Training European Experts in Multiscale Studies of Neural Crest Development and Disorders: from Patient to Model Systems and Back again.

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2019-11-01 → 2024-04-30
EU contribution
€4,156,405
Participants
11
Scheme
MSCA-ITN

Lines connect the coordinator with its partners.

Results in brief

Training European Experts in Multiscale Studies of Neural Crest Development and Disorders: from Patient to Model Systems and Back again.

The neural crest (NC) lineage, deriving from the multipotent and migratory embryonic NC cell population, contributes to form the peripheral nervous system, craniofacial structures, pigment cells and many other tissues and organs in vertebrates, from lamprey to human. Anomalies in NC formation are associated with approximately one third of human congenital malformations and syndromes such as cleft lip/palate, syndromic craniosynostosis, Hirschsprung Disease, Waardenburg syndrome and Pierre Robin Sequence. Furthermore, in Europe, cancers of NC derivatives, e.g. neuroblastoma, pheochromocytoma and malignant melanoma cause 7-10% of childhood cancers and 3-7% of cancer deaths respectively. Thus, diseases of NC-derived tissues, referred to as neurocristopathies, are an acute societal problem. Due to the complexity of these tissues, understanding the underlying causes and mechanisms requires multi-disciplinary expertise. To address this, we require the dedicated training of a new generation of scientists and clinicians, working with academia and industry. Only in this way can we broaden our scope, working power and understanding of the impact of neural crest biology in health and disease. The NEUcrest project aimed at training 15 ESRs within a novel, ambitious and interdisciplinary research program, which main objectives were 1) to undertake an integrated gene discovery approach in NC development and neurocristopathies; 2) to establish cellular and animal models for neurocristopathies with complementary experimental advantages while implementing ethical recommendations; 3) to analyse the function of genes involved in human neurocristopathies with optimised integrative strategies; 4) to establish reciprocal links between clinical genetics and functional studies of neurocristopathies; 5) to establish biostatistical strategies tailored for NC gene network computational modelling; 6) to optimize NC differentiation from human stem cells in order to reach industrial standards; 7) to establish the best translational strategies for drug screening in NC-related diseases; 8) to disseminate results for implementation of best practices for molecular diagnostic management strategies; and, 9) to increase awareness about neurocristopathies in the general public.

Data: CORDIS, © European Union

Project objective

Neurocristopathies caused by defects in the neural crest (NC) encompass a broad group of diseases from birth defects (cleftvpalate) to complex syndromes affecting systems such as heart, gut and adrenals. Because NC derivatives are diverse, mutations affecting this lineage can lead to pleiotropic phenotypes making it difficult to understand the causative events. Furthermore, NC-derived cancers, (e.g. melanoma and neuroblastoma) reactivate embryonic programs during tumour initiation. Our aim is to create a unique interdisciplinary network of scientists and clinicians partners from academia, healthcare, industry and the public sector with experience in gene discovery, genetics, functional studies and in vivo phenotyping aimed at training creative and innovative ESRs to study the overall genetic, molecular and environmental regulation of NC tissue in human health. To study each of complex aspects of NC and tumour formation, NEUcrest provides a synergistic framework for comprehensive analysis of candidate genes and biological processes, from patients to model systems to pharma and back to the clinic. With the aim to develop a unified strategy to identify new genetic and environmental factors that contribute to disease and to develop new drug targets for therapeutics, ESRs will address following scientific challenges: undertake novel gene discovery approaches; establish cellular/animal models of disease; establish integrative strategies for understanding neurocristopathies; optimise computational modelling of NC gene networks; establish translational strategies for drug screening in NC-related diseases; improve clinical management strategies of NC-disease and interface with patients and the public. Our training program takes into account training through research as well as multidisciplinary partnerships and networking opportunities. All together, this will improve our understanding of the fundamentals of neurocristopathy and contribute to improvements in healthcare.

Original text from CORDIS.

Participants

  • INSTITUT CURIE · ParisCoordinatorFrance
  • AZELEAD · MontpellierFrance
  • ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM · RotterdamNetherlands
  • IMAGINE INSTITUT DES MALADIES GENETIQUES NECKER ENFANTS MALADES FONDATION · ParisFrance
  • KING'S COLLEGE LONDON · LondonUnited Kingdom
  • MEDIZINISCHE UNIVERSITAET WIEN · WienAustria
  • STEMCELL TECHNOLOGIES UK LTD · CAMBRIDGEUnited Kingdom
  • TEL AVIV UNIVERSITY · Tel AvivIsrael
  • UNIVERSIDAD MIGUEL HERNANDEZ DE ELCHE · ElcheSpain
  • UNIVERSITY OF EAST ANGLIA · NorwichUnited Kingdom
  • UNIVERSITY OF GALWAY · GalwayIreland

Links

Data: CORDIS, © European Union