Objective
Chronic liver inflammation has been shown to promote hepatocellular carcinoma (HCC). However, the initial cellular and molecular events that trigger the inflammation are largely unknown. The proposed study will provide a detailed characterisation of cellular processes that need to be deregulated in liver cells to cause inflammation. For this purpose, a genetic mouse model that closely reproduces all the stages of inflammation-related HCC will be used. This mouse exhibits a Liver Parenchymal Cell specific NEMO ablation (NEMOLPC-KO), the regulatory subunit of the IKK complex that activates NF-kB signalling.
The two main goals of the proposed project are to a) unravel early cellular and molecular alterations in the liver cells of NEMOLPC-KO mice, and distinguish these resulting from a cell-autonomous effect of NEMO deletion from those resulting from a non-cell autonomous effect due to the inflammatory microenvironment and b) distinguish between NF-kB-dependent and independent functions of the NEMO/IKK complex in liver homeostasis.
Two experimental strategies will be used to achieve these goals. The first is a targeted examination of specific cellular processes that could be implicated in the development of liver inflammation, such as the mitochondrial functions, ER stress, autophagy, and p62 functions. A combination of mouse genetics with cutting-edge microscopy and other cell biology techniques will be employed. The second involves high-throughput approaches, such as gene expression microarray, that will help distinguishing between the above-mentioned NEMO functions.
The scientific impact of this study will be to define early cellular changes can disrupt liver cell homeostasis resulting in human liver inflammatory diseases, thus helping in development of new therapeutic approaches. Finally, the project will greatly benefit the applicant’s professional maturity that is important for pursuing an independent research career.
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 genetics
- medical and health sciences health sciences inflammatory diseases
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics microscopy
- 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.
FP7-PEOPLE-2010-IEF
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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.
Coordinator
50931 KOLN
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.