Objective
Induced pluripotent stem cells (iPSCs) are expected to have an enormous impact on medical research. However, the efficiency of reprogramming is still low and far from routine. Nevertheless, reprogramming with defined factors, Oct4, Sox2, Klf4 and c-Myc, is not a random event. Cells positive for SSEA-1, a marker of undifferentiated mouse ES cells (ESC), appear from cells which have lost the fibroblast marker Thy-1, prior to acquiring other pluripotent markers, e.g. Oct4, Nanog. Similarly, TRA-1-60 positive fully reprogrammed human iPSCs appear from SSEA-4 positive populations. Based on these observations, I hypothesize that there are essential ordered stages that the cells must undergo as they are directed toward pluripotency.
To explore this hypothesis, I plan to perform three projects:
1. Identifying gene expression signatures during the successful reprogramming process.
2. Investigating serial changes of reprogramming factor binding, chromatin modifications and chromatin structure on the route to a pluripotent state.
3. Functional analysis of the candidate gene(s) identified for successful reprogramming.
Based on my latest publication in Nature, I have developed an original highly efficient reprogramming system, in which almost all cells differentiated by retinoic acid treatment generate iPSCs by day 12 post reprogramming factor induction. The homogenous culture allowed by this system enables the unique execution of the objectives above, and for the first time will shed light on the molecular mechanisms of the reprogramming process. Accurate and more informed understanding of these ordered processes will allow derivation of strategies to improve the reprogramming technology.
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 medical biotechnology cells technologies stem cells
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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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-2010-StG_20091118
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
EH8 9YL Edinburgh
United Kingdom
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.