Periodic Reporting for period 1 - NEUcrest (Training European Experts in Multiscale Studies of Neural Crest Development and Disorders: from Patient to Model Systems and Back again.)
Reporting period: 2019-11-01 to 2021-10-31
The neural crest (NC) lineage is a specialised multipotent embryonic tissue, which contributes notably to the development of the human peripheral nervous system, craniofacial structures, pigment cells, as well as many other tissues and organs. Due to its broad contributions during embryonic development, it is likely that NC dysfunction contributes to many of the congenital malformations seen in live births in Europe (up to one third of live births with congenital defects may involve NC anomalies), including, for example, cleft lip/palate, syndromic craniosynostosis, Hirschsprung Disease, Waardenburg syndrome and Pierre Robin Sequence. Furthermore, in Europe, cancers of NC derivatives including 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 a whole as neurocristopathies, are an acute societal problem that can now be tackled by a combination of multiscale and multidisciplinary strategies, but require the dedicated training of a new generation of scientists and clinicians, to work in both academia and industry.
The aim of the NEUcrest project is to train 15 creative and innovative ESRs within a novel, ambitious and interdisciplinary research program, which main objectives are the following:
1. To undertake an integrated gene discovery approach in NC development and neurocristopathies;
2. To establish cellular and animal models of neurocristopathies with complementary experimental advantages while implementing ethical recommendations;
3. To analyse the role 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;
9. To increase awareness about neurocristopathies in the general public.
The aim of the NEUcrest project is to train 15 creative and innovative ESRs within a novel, ambitious and interdisciplinary research program, which main objectives are the following:
1. To undertake an integrated gene discovery approach in NC development and neurocristopathies;
2. To establish cellular and animal models of neurocristopathies with complementary experimental advantages while implementing ethical recommendations;
3. To analyse the role 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;
9. To increase awareness about neurocristopathies in the general public.
During the first half of the NEUcrest project, the fifteen early-stage researchers have been trained in the various fields necessary to understand these complex scientific questions, in the technical approaches used in their host laboratories, and advanced in the discovery of candidate genes for neural crest-linked disorders. Firstly, using a patient-centred approach they have selected genes associated with human neurocristopathies. Secondly, through a neural crest gene regulatory network approach, they have identified and selected novel candidates supporting specific mechanisms of neural crest induction, cell migration, differentiation or tumour transformation. This has generated a list of more than 500 gene candidates, which have been prioritised-down to 100 genes, several of which of interest for many partners of the network, thus stimulating collaborative works. Expression and functional analyses of these genes has been further narrowed down to the most promising factors and is currently under detailed analyses using patient-derived cells or animal models. Communication and outreach about the project has taken various forms so far: specialized publications of research results and scientific reviews (6), conference posters (2), European Researcher’s Night 2021 participation (2), accessible materials published on our Project’s website and via social media (11 recordings and multiple threads). Our major anticipated milestone towards which the work has started is to prepare the Neural Crest section update to the public Wiki-based encyclopaedia on Human embryology.
NEUcrest network effectively puts together a pipeline from clinic to the bench to the pharmaceutical company and, in the end, back to the patient via personalised medicine (e.g. hiPSCs and organoids). Because this is built into our training programme, we expect that this will have a massive impact for the public, especially for those suffering from rare diseases.
Neurocristopathies include dramatic anomalies (craniofacial and other malformations) that have a strong impact on the life of affected individuals. Society’s awareness of these diseases is slowly rising, but the acceptance of handicap in everyday life still requires education. The recent movie « Wonder», about a child bearing the Treacher Collins neurocristopathy exemplifies this hesitatingly emerging consciousness. Addressing affected patients and patient’s families requires dedicated training. NEUcrest aims to offer a unique opportunity to the 15 young scientists to learn how to present their research to different audiences, from teenagers to patients, from academic science actors to industrialists. Together the NEUcrest network will provide new and synthetic data to a wide range of professionals and to patients and public
Neurocristopathies include dramatic anomalies (craniofacial and other malformations) that have a strong impact on the life of affected individuals. Society’s awareness of these diseases is slowly rising, but the acceptance of handicap in everyday life still requires education. The recent movie « Wonder», about a child bearing the Treacher Collins neurocristopathy exemplifies this hesitatingly emerging consciousness. Addressing affected patients and patient’s families requires dedicated training. NEUcrest aims to offer a unique opportunity to the 15 young scientists to learn how to present their research to different audiences, from teenagers to patients, from academic science actors to industrialists. Together the NEUcrest network will provide new and synthetic data to a wide range of professionals and to patients and public