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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine physiology homeostasis
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-StG
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
7610001 Rehovot
Israel
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.