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Investigating genotype-phenotype correlations in SOX10 neurocristopathies

Objective

Neural crest formation is a critical event in development, giving rise multiple cell types including melanocytes, neurons and glia. This complex process is governed by a network of transcription factors, such as PAX3 and SOX10 and mutations in these genes have been associated with developmental syndromes. Waardenburg syndrome (WS) and Hirshsprung disease are examples of these neurocristopathies and patients suffer symptoms ranging from sensorineural hearing loss and pigmentation defects to intestinal aganglionosis. Over 50 case studies of WS have been reported in Europe and the incidence is estimated to be 1 in 42 000 people. Recent investigations into the molecular basis of WS have failed to identify genotype-phenotype correlations between gene mutations and symptoms, likely due to the in vitro nature of these studies. It has therefore become clear that new tools are needed to better understand the genotype-phenotype relationship in neurocristopathies in an in vivo context. The SOX10mutants project proposes to address this using a novel zebrafish rescue assay to investigate the effects of SOX10 mutations on the development of cell types deriving from the neural crest. Results from this study would impact significantly on genetic counselling and pre-natal screening of WS patients and provide proof-of-concept data for the use of zebrafish as a tool for studying neurocristopathies. This project is the basis of a multi-disciplinary collaboration between Prof. Robert Kelsh (University of Bath, UK) and Dr Nadège Bondurand (INSERM, France), bringing together zebrafish expertise with WS clinical genetics experience. The research fellow, Dr Deeya Ballim, contributes transcription factor knowledge and a diverse skill set. Deeya aims to establish an independent research group and this fellowship will be a key step in her career development, by expanding her research and academic training, supported by Prof. Kelsh and the University of Bath.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2014

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Coordinator

UNIVERSITY OF BATH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 195 454,80
Address
CLAVERTON DOWN
BA2 7AY BATH
United Kingdom

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Region
South West (England) Gloucestershire, Wiltshire and Bristol/Bath area Bath and North East Somerset, North Somerset and South Gloucestershire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 195 454,80
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