Obiettivo The mammalian liver performs critical functions for maintaining metabolic homeostasis. It regulates the body’s glucose and lipid stores, detoxifies blood, and produces bile among a host of other functions. The liver achieves this diversity through the collective behaviour of heterogeneous hepatocytes operating in highly structured microenvironments. Understanding the design principles of the liver is an open challenge requiring analysis of single cells within the intact tissue.Liver heterogeneity appears at two length scales. At the liver lobule level centripetal blood flow creates gradients of oxygen, nutrients and hormones. The consumption of hepatocytes along the lobule axis determines the inputs available for more centrally located hepatocytes. The resulting spatial division of labor, termed ‘liver zonation’ could enable optimal tissue function in face of these long-range constraints. At the cellular level most hepatocytes are polyploid cells, having either one or two nuclei and a corresponding variability in cell sizes. The functional advantage of liver polyploidy remains unclear.In this proposal we aim to combine single molecule transcript imaging in the intact liver with theory from systems biology to uncover the design principles of liver heterogeneity. We will examine the hypothesis that spatial zonation and hepatocyte polyploidy evolved to enable the liver to optimally operate. We will characterize the spatial co-expression patterns of key liver genes and theoretically compare the ability of these patterns to excel over alternative patterns. We will also characterize the differential resource allocation of hepatocytes of different ploidy classes.This interdisciplinary project stands at the forefront of research in mammalian biology, addressing fundamental properties of a major organ at unprecedented single-cell resolution. It will open new avenues for extending the field of systems biology to the analysis of complex tissues in mammalian organisms. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesbasic medicinephysiologyhomeostasis Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS2 - ERC Starting Grant - Genetics,Genomics,Bioinformatics and Systems Biology Invito a presentare proposte ERC-2013-StG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante WEIZMANN INSTITUTE OF SCIENCE Contributo UE € 1 500 000,00 Indirizzo HERZL STREET 234 7610001 Rehovot Israele Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gabi Bernstein (Ms.) Ricercatore principale Shaul Shalev Itzkovitz (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto WEIZMANN INSTITUTE OF SCIENCE Israele Contributo UE € 1 500 000,00 Indirizzo HERZL STREET 234 7610001 Rehovot Mostra sulla mappa Tipo di attività Higher or Secondary Education Establishments Contatto amministrativo Gabi Bernstein (Ms.) Ricercatore principale Shaul Shalev Itzkovitz (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato