LIVHET
Single cell heterogeneity in the mammalian liver
| Coordinatore | WEIZMANN INSTITUTE OF SCIENCE
Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie. |
| Nazionalità Coordinatore | Israel [IL] |
| Totale costo | 1˙500˙000 € |
| EC contributo | 1˙500˙000 € |
| Programma | 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) |
| Code Call | ERC-2013-StG |
| Funding Scheme | ERC-SG |
| Anno di inizio | 2013 |
| Periodo (anno-mese-giorno) | 2013-11-01 - 2018-10-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
WEIZMANN INSTITUTE OF SCIENCE
Organization address
address: HERZL STREET 234 contact info |
IL (REHOVOT) | hostInstitution | 1˙500˙000.00 |
| 2 |
WEIZMANN INSTITUTE OF SCIENCE
Organization address
address: HERZL STREET 234 contact info |
IL (REHOVOT) | hostInstitution | 1˙500˙000.00 |
Mappa
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Obiettivo del progetto (Objective)
'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.'