Date: Friday, November 17th | Serratosa | 17|11|2023 Time: 10:00 AM Speaker: Dr. Carlos Pardo Pastor…
Date: Friday, March 24th | Felix Serratosa room | 24|03|2023
Time: 10:00 AM
Speaker: Leonardo Beccari.
Ramon y Cajal researcher at the CBMSO.
Title: “Organoid-based approaches to address the transcriptional regulation of human cortex development“
Host researcher: Dr. Murielle Saade
The transcriptional regulation of gene expression holds a central role in the control of developmental processes, and mutations affecting the activity or interactions of regulatory sequences can lead to severe developmental alterations. Next-generation sequencing approaches have led to the annotation of over 1,000,000 non-coding sequences with regulatory potential in the human genome. However, their functional role and their contribution to gene expression and embryonic structure development remain, in the vast majority of the cases, unexplored. Our research focuses on addressing the transcriptional mechanisms underlying normal and pathogenic human cortex development. However, the divergence of our non-coding genome and the anatomico-developmental specificities of the human cortex compared to that of other mammalian/ vertebrate models strongly limit the study of human neurodevelopmental gene regulation. We have implemented an efficient and reliable recombination-driven enhancer transgenesis approach for the characterization of enhancer activity in organoids, and we are applying it to characterize the cis- regulatory code controlling the expression of the human TBR2 gene (aka EOMES), a transcription factor which plays an essential role in the cortical neurogenic process. Besides, we are combining CRISPR/Cas9 genome editing and chromatin epigenetic and transcriptional profiling of cortical neural precursors to address the role of the chromatin remodeler CHD2, an epigenetic modifier whose mutations in humans are associated with epilepsy, autsism and other neurodevelopmental alterations.
Leonardo Beccari is a Ramon y Cajal researcher at the CBMSO. He performed his PhD thesis in the laboratory of Paola Bovolenta (Madrid), addressing the gene regulatory networks (GRN) that control vertebrate forebrain patterning. After his PhD thesis, he joined the laboratory of Denis Duboule (University of Geneva) where he investigated how the interplay between chromatin 3D organization and enhancer activity contribute to the spatio-temporal regulation of developmental genes and how new gene regulatory innovations can arise by de novo acquisition of enhancers and hijickaing of an evolutionary conserved chromatin architecture. Finally, he contributed to the implementation and characterization of gastruloid cultures: 3D aggregates which recapitulate the for the study of early embryonic development (3D cultures which recapitulate early embryonic development, a work that constituted a ground-breaking piece of research in the organoid field. In 2020, he established as junior PI at Institute NeuroMyoGene (Lyon), addressing the transcriptional mechanisms that control neurodevelopmental gene expression in the human embryonic cortex and how regulatory mutations relate to congenital brain alterations/disorders and to the of brain evolution. To investigate these questions his team focuses on (i) the characterization of the cis-regulatory elements (CREs) driving neurodevelopmental gene expression and of role of chromatin 3D organization, and (ii) the study of the epigenetic mechanisms controlling the activity of regulatory sequences. In 2022, he joined the CBMSO awarded with a Ramon y Cajal contract.
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