Objective
Keratin intermediate filaments are cytoskeletal proteins regulating the polarity and intracellular organization of epithelial cells, influencing interactions of epithelia with the surrounding environments. This is particularly relevant in the intestine, where a single cell layer of epithelial cells form a barrier between the luminal content and the underlying tissues. Keratin 8 (K8) null mice develop an ulcerative colitis-like inflammatory bowel disease (IBD) that responds to antibiotic therapy. K8 null colonocytes also mistarget ion transporters in association with abnormal chloride transport and diarrhea. The unexpected connection between K8 and colitis led to a proteomic approach, showing decreased expression of the ketogenic enzyme mHMG-CoAs in K8 null colonocytes. K8 null mice also develop autoantibodies against mHMG-CoAs. These findings raise the hypothesis that colonic keratins modulate ketone body metabolism, which is relevant to the IBD phenotype, since bacteria regulate mHMG-CoAs through butyrate, a major colonocyte energy source. The aims are to use microarray data to identify differences in K8 null ketone body metabolism and verify findings by inducing ketogenesis and measuring the ramifications of a blunted pathway. Mistargeting of butyrate transporters will also be investigated. K8 mutations predispose to liver disease but the role in IBD is unknown. Apart from contributing to the understanding of the biological roles of keratins, including ketone body metabolism, the study has broad ramifications for patients suffering from the common and incapacitating IBD-conditions, for patients with keratin mutations, and may aid in developing diagnostic/therapeutic modalities. I wish return to Europe and establish myself as a Finnish investigator after advanced training at Stanford University. The Turku-BioCity environment combined with my unique skills and collaborative networks with Stanford University provide excellent prospects for a fruitful synergy.
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.
- natural sciences chemical sciences organic chemistry ketones
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine hepatology
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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-2007-4-3-IRG
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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
20500 Abo
Finland
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.