Objective
A fundamental property of animal cells is the ability to maintain their volume constant to face changes in osmolarity and during division, migration and transepithelial transport. There is emerging evidence that cell swelling also initiates signaling cascades that regulate metabolism, particularly in hepatocytes. However, the basic mechanisms responsible for sensing volume changes and initiating volume-regulated signaling cascades in the liver remain largely unclear. As major player in cell volume regulation, the Volume-Regulated Anion Channel VRAC may influence liver metabolism by controlling hepatocyte volume. VRAC was recently identified by the host laboratory as LRRC8 heteromers. LRRC8A represents the obligatory subunit and forms heteromers with LRRC8B-E isoforms. Depending on the subunit composition, the heteromers present specific electrophysiological properties and transport different substrates.
The aim of this proposal is then (i) to investigate the role of VRAC and its different subunits in liver function and particularly (ii) as signal transducer between hepatocyte volume and metabolism.
The host laboratory already generated numerous LRRC8 mouse models e.g. tagged-Lrrc8 knock-in mice which are valuable tools to determine the subcellular distribution of the different LRRC8 subunits in the liver. I will also develop hepatocyte-specific knock-out (KO) mice to analyze the liver histology and function. Primary hepatocytes from the different KO will be used to study the potential roles of VRAC in liver physiology at the cellular level e.g. via autocrine signaling cascades. I finally intend to identify the VRAC-dependent hepatic metabolic pathways using large-scale analytical techniques and evaluate the systemic metabolism of the different KO mice. My project is expected to uncover the role of VRAC in liver physiology from molecular to systemic level and thus to provide detailed insights of the molecular coupling between hepatocyte volume and liver metabolism.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine physiology
- natural sciences biological sciences histology
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF-EF-ST - Standard EF
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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.
(opens in new window) H2020-MSCA-IF-2017
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
13125 Berlin
Germany
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.