PRBB-CRG Sessions Masatoshi Hagiwara Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto JP Challenges to cure genetic disorders with "RNA-targeting" chemical compounds
Host: Juan Valcárcel (CRG)
Abstract: Patients of congenital diseases have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by mis-splicing resulting from an intronic mutation in IKBKAP gene. FD would be treatable if we can develop "a splicing modulator" which promotes exon20 inclusion of IKBKAP and increases the expression of IKAP protein in FD patient cells. In order to find the modulator, we established splicing reporter assay with dual color (SPREAD) using a segment of human IKBKAP spanning from exon19 to exon21. SPREAD allows us to visualize the splicing in cells, and to identify RBM24 and RBM38 as the tissue-specific modulators for exon20 inclusion of IKBKAP. This also enabled us to find a chemical compound RECTAS, which can rectify the aberrant IKBKAP splicing in FD patient fibroblasts. Our data implicate the mis-splicing of IKBKAP in the reduced tRNA modification in FD patient and demonstrated that RECTAS could be the therapeutic drug.
PRBB-CRG Sessions Juli Peretó Evolutionary Genetics, Institut Cavanilles de Biodiversitat i Biologia Evolutiva, University of Valencia ES "Metabolic innovation by endosymbiosis"
Host: Jaume Bertranpetit (UPF)
Abstract: Juli Peretó is Tenured Professor of Biochemistry and Molecular Biology at the University of València, researcher at the Evolutionary Genetics Unit, Cavanilles Institute for Biodiversity and Evolutionary Biology and member of Institut d’Estudis Catalans. His research interests include the evolution of metabolism, the minimal genome concept, and the history of ideas on the natural origin and the artificial synthesis of life. He teaches metabolism with an evolutionary flavor to biologists, biochemists and biotechnologists. He was formerly Secretary of the International Society for the Study of the Origin of Life (ISSOL) and has been elected as Second Vice President of ISSOL for the term 2011-2014. During the period 2012-14 he has been coordinator of the Erasmus Intensive Program “Origin, Evolution, and Future of the Biosphere”. He is also Field Editor for Biochemistry of the Encyclopedia of Astrobiology (Springer, 2012). His most recent book, coauthored with A. Moya, is “Simbiosis: seres que evolucionan juntos” (Síntesis, Madrid, 2011), and at the end of this year will appear “Synthetic Biology: From iGEM to the Artificial Cell” coauthored with Manuel Porcar (Springerbriefs, forthcoming).
PRBB-CRG Sessions James Brugarolas Developmental Biology, Internal Medicine, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas (TX) US "Towards a molecular genetic and functional classification of renal cancer"
PRBB-CRG Sessions Kostas Stamatopoulos Laboratory of Cellular and Molecular Biology, Institute of Applied Biosciences, CERTH, Thessaloniki GR "Immunogenetics of B-cell lymphomas: linking sequences with functional outcomes"
PRBB-CRG Sessions Robert Schneider Functional Genomics & Cancer, Institut de Génétique et de Biologie Moleculaire et Cellulaire (IGBMC), Illkirch FR "Novel Players in Chromatin"
Host: Luciano di Croce (CRG)
Abstract: One of the major goals of post-genomic biological research is to understand the molecular basis and physiological role of covalent protein modifications. These post-translational modifications (PTMs) can regulate protein interactions and/or stability and thus trigger particular downstream responses. The best-characterised substrates for multisite PTMs are currently the histone proteins. Two of each of the four core histones (H3, H4, H2A and H2B) form the nucleosomal core particle around which 147 bp of DNA are wrapped. It has been suggested that PTMs of histones constitute a so-called "histone code". Nonetheless the set of characterised histone modifications is far from complete and many modifications are awaiting identification. PTMs of histones are also clinically very important. Histone modifying enzymes have been found to be rearranged, mutated or deleted in many different types of. In particular the reversible nature of PTMs has led to the emergence of the promising field of epigenetic therapy. One of key questions in the field is if histone PTMs can be causative for processes like transcription or are just by-products, with limited functional relevance. We recently demonstrated a causative function for lysine acetylation on the lateral surface of the histone octamer. We found that acetylations within the core of the nucleosome at positions that are in contact with the DNA are sufficient to stimulate transcription by modulating histone-DNA binding. Our model is that nucleosome function and signaling to the epigenome is directly regulated by specific lateral surface modifications. Furthermore, we identified additional novel PTMs that act as guardian of genome stability by regulating the activity of transposable elements.