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Giovanni D’Angelo Institute of Protein Biochemistry National Research Council of Italy Abstract: Glycosphingolipids (GSLs) are a heterogeneous group of membrane lipids that are formed by a ceramide backbone covalently linked to a glycan moiety. Hundreds of different glycans can be linked to ceramide, giving rise to an astonishing variety of structurally different compounds. The GSL glycan ‘sequences’ are not strictly genetically determined, but rather depend on the configuration of the GSL synthetic machinery, and confer to these compounds high theoretical information content, which is exploited by the cells to store and transmit biological messages. Indeed, individual GSLs interact with and modulate specific plasma-membrane receptors, and in this way contribute to cell signalling. Importantly, although GSLs are dispensable for cellular life, they are collectively required for the development of multicellular organisms, and are thus considered to be key molecules in ‘cell sociology’. All these properties position GSLs among the cellular factors that impact on the organism phenotype at a non-genetic level. However, in contrast to other classes of molecules that share similar properties, little is known about the targets of GSL regulation, the control of GSL expression, and the possible metabolic and genetic circuits that integrate GSLs with other cell-regulatory elements. In other terms, glycan sequences in GSLs can be seen as a biological ‘language’, that is used by cells to specify their identities in multicellular contexts; the meaning and grammar of this language remain to be interpreted. With this project I propose to study the molecular mechanisms and physiological implications of the GSL profiles, by interrogating the control circuits and gene networks influenced by specific GSL configurations. With this aim, I will take a systems biology approach combining cell biology, lipidomics, transcriptomics, and phosphoproteomics to infer a tentative map of the GSL regulatory landscape after specific perturbations of the GSL profile in model cells. Short cv Positions: 2011-present Researcher at Institute of Protein Biochemistry – National Research Council of Italy. Naples. 2010-2011 PostDoc at Telethon Institute for Genetics and Medicine (TIGEM), Naples. 2008-2009 PostDoc at Consorzio “Mario Negri” Sud, Santa Maria Imbaro 2004-2008 PhD Student at Consorzio “Mario Negri” Sud, Santa Maria Imbaro 1999-2003 Undergraduate Research trainee. Dept. of Biochemistry and Medical Biotechnology (DBBM), Medical School, University of Naples “Federico II”, Naples. Recent publications : Glycosphingolipids: synthesis and functions D’Angelo G, Capasso S, Sticco L, Russo D. FEBS jounal 2013 Dec;280(24):6338-53 Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi. D'Angelo G et al. Nature. 2013 Sep 5;501(7465):116-20 Connecting vesicular transport with lipid synthesis: FAPP2. D'Angelo G, Rega LR, De Matteis MA. Biochim Biophys Acta. 2012 Aug;1821(8):1089-95. Phosphatidylinositol-4-phosphate: the golgi and beyond. De Matteis MA, Wilson C, D'Angelo G. Bioessays. 2013 Jul;35(7):612-22 Identification of microRNA-regulated gene networks by expression analysis of target genes. Gennarino VA, D'Angelo G, et al. Genome Res. 2012 Jun;22(6):1163-72 Phosphoinositides in Golgi complex function. D'Angelo G, Vicinanza M, Wilson C, De Matteis MA. Subcell Biochem. 2012;59:255-70.