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.
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