PROJECT: JTC2021: EPINEURODEVO

Patient-centered Targeting of Epigenetic Vulnerabilities in Neurodevelopmental Disorders: A Cross-disciplinary Platform for Druggable Disease Models

Abstract

Intellectual disability disorders (IDDs) represent a spectrum of neurodevelopmental disorders characterized by early childhood onset of learning impairment behavior defects. IDDs are linked to detrimental factors that affect cortical development. Many mutations that cause IDDs have been identified. They represent pathways linked to synaptic function and epigenetic gene-expression control Since epigenetic gene-expression is a key process controlling neuronal function in the developing and adult brain targeting the epigenome could be a promising strategy to treat IDDs. Our overarching aim is to better understand the epigenetic vulnerabilities in neurodevelopmental diseases with a specific focus on IDDs that share the genetic and epigenetic de-regulation of H3K4 methylation. We will perform, for the first time, a truly systematic analysis of H3K4-related processes across the spectrum of IDDs ranging from epigenetic gene-expression changes to the corresponding functional consequences. Our consortium is in a perfect position for this task as it combines the unique expertise in epigenetics, brain development, neuronal structural and functional plasticity with ample experience in modeling IDDs in mouse models, iPSC derived human brain organoids in xenograft models. Our results will provide a blueprint for translation research in neurodevelopmental diseases and could have immediate clinical impact.

Keywords

Molecular modelling techniques, epigenetic, Stem Cells, Electrophisiological approaches, Behavioural methodologies, (epi)genetic approaches, omics approaches, Animal studies, intellectual disability disorders, histone-methylation, human brain organoids, xenograft models, H3K4

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Andre Fischer (Coordinator)
Germany (BMBF)
Guiseppe Testa
Italy (MOH)
Angel Barco
Spain (AEI)
Shlomo Wagner
Israel (CSO-MOH)
Pierre Vanderhaeghen
Belgium (FWO)
Zoltán Mészár
Hungary (NKFI)