Project: Chromatin-related intellectual disability syndromes: Molecular etiology and therapy

Acronym	ChromISyn
Duration	07/02/2016 - 28/02/2019
Project Topic	Intellectual development disorders (IDDs) represent one of the biggest medical challenges in our society. Their cause includes the mutation of genes encoding epigenetic regulators of gene expression. IDD-linked epigenetic factors often interact with one another in complexes that regulate chromatin structure at genes important for neurodevelopment and/or neuroplasticity. This proposal focuses on Rubinstein-Taybi syndrome (RSTS), a rare autosomal dominant disorder caused by mutation in the genes encoding the lysine acetyltransferases CBP and p300. Our main objectives are: (i) To dissect the developmental and adult components of RSTS and the anatomical substrate of cognitive impairment; (ii) to determine the differential roles of CBP and p300 in neuronal plasticity and neurodevelopment; (iii) to generate the first inducible pluripotent stem cells (iPSCs) from RSTS patients; (iv) to identify the epigenetic and transcriptional alterations that underlie RSTS through state-of-the-art genomic screens conducted in mouse models of the disease and in iPSC-derived neurons from human patients; and (v) to assess novel epigenetic editing tools aimed to correct the alterations retrieved in our genomic screens. Since other chromatin-related IDDs target common gene networks, the impact of our project goes well beyond RSTS and can also contribute to the understanding and therapy of other IDDs, as well as answer fundamental questions in neurobiology.
Network	ERA-NET NEURON II
Call	Neurodevelopmental Disorders

Project partner

Number	Name	Role	Country
1	Universidad Miguel Hernandez de Elche	Coordinator	Spain
2	Istituto Auxologico Italiano	Partner	Italy
3	University of Haifa	Partner	Israel
4	Agencia Estatal Consejo Superior de Investigaciones Científicas	Partner	Spain