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Multi-Omics Brain Organoid dissection of Dravet Syndrome

Project description

Personalised therapies for Dravet Syndrome patients

Dravet Syndrome (DS) is a severe childhood epilepsy characterised by recurrent seizures and developmental delays. Most patients have SCN1A gene mutations, but outcomes vary due to other factors. The impact on different brain cells and their responses to the disease are still unclear. With the support of the Marie Skłodowska-Curie Actions programme, the MOBODS project will map disrupted molecular pathways in DS at single-cell resolution using brain organoid models, multi-omics data and computational methods. It will identify cell-type-specific transcriptional changes, map gene regulatory network perturbations and characterise metabolic dysfunctions. By linking the genetic basis of DS to its clinical variability, MOBODS will develop more personalised therapies for DS patients resistant to conventional treatments.

Objective

Dravet Syndrome (DS) is one of the most severe developmental epileptic disorders in children, characterized by spontaneous recurrent seizures, developmental delay, and high risk of premature death. While approximately 80% of patients carry loss-of-function mutations in the SCN1A gene, clinical outcomes vary significantly, suggesting that other molecular and cellular factors influence disease manifestation. Although we know this mutation impairs inhibitory neuron function, it remains unclear 1) which other brain cell types are affected and 2) how these cells respond to the pathogenic environment by altering their genome regulation and cellular metabolism. MOBODS aims to map disrupted molecular pathways in DS at single-cell resolution, using a multidisciplinary approach that integrates brain organoid models, time-series multi-omics data, and computational methods. This research tackles three key challenges: identifying cell type-specific transcriptional changes, mapping gene regulatory network perturbations, and characterizing metabolic dysfunctions. By linking the genetic basis of DS with its clinical variability, these results can help develop in the long term more personalized therapies, particularly important as over 50% of DS patients are currently resistant to conventional treatments and require multiple anti-seizure medications. Furthermore, improved molecular characterization of DS symptoms can help reduce the stigma associated with epilepsy. Standardizing and validating the terminology used to describe symptoms can support patients in overcoming both interpersonal and institutional stigma, such as challenges in social interactions or discrimination in employment and insurance policies. Through this project, I will gain independence in experimental research, expertise in large-scale genetic studies, and leadership skills—all crucial for securing a tenure-track position in molecular and computational biology and effectively managing research resources.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITAT DE BARCELONA
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.

€ 194 074,56
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost

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