Objective
Background: Our recent studies implicate p53 in gut tissue homeostasis - suppressing epithelial invasion. This function is tightly linked to suppression of a gene cluster (PSIS- p53-Suppressed Invasiveness Signature), which requires Wnt activation and other cues, yet is only expressed upon loss of p53. The invasive signature explains a broad spectrum of the invasiveness property, from the loss of enterocyte polarity to matrix degradation, pointing to a concerted action. We documented a tight association between invasiveness and coexpression of several PSIS genes in different mouse models and showed that PSIS expression is essential in mediating epithelial cell invasiveness following p53 depletion.
Goal: Elucidate functions of p53 activation which are of particular importance for epithelial tissues. Understand how WT p53 contributes to preserving epithelial boundaries, prohibiting invasion and abnormal cell mixture and controlling stem cell dynamics under tissue stress.
Methodology: We will investigate the epithelial role of p53 and the invasive signature genes in several mouse models of inflammatory bowel diseases and intestinal cancer. These models will incorporate p53-modulating switchable genetic elements and cell-tracking genetic markers for monitoring tissue dynamics. Analyses of relevant human pathology samples will complement the mouse studies.
Significance: Invasion is a defining hallmark of malignancy and understanding early invasion of tumor cells is of fundamental importance in designing future therapies for cancer - targeting PSIS is an example. PSIS database may also be used to develop biomarkers for distinguishing malignant tumors from benign ones, a critical determinant of therapeutic options in several types of cancers, currently solely based on morphologic assessment. A molecular definition of early invasive lesions may allow early implementation of curative treatments while withholding patient overtreatment which often results in serious morbidity.
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.
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology
- medical and health sciences basic medicine pathology
- 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-2011-ADG_20110310
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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.
Host institution
91904 JERUSALEM
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.