Objective
Mammalian haematopoiesis in the adult takes place predominantly in the bone marrow (BM) where a population of haematopoietic stem cells (HSC) are located. HSC are able to self-renew and give rise to all the blood cell types. The fate choice of HSC to either self-renew or differentiate is controlled by an interplay between intrinsic mechanisms and extrinsic signals from the surrounding environment called stem cell niche. The existence of a hypoxic niche in the BM has been highlighted in the last decade. It has been proposed that the most quiescent HSC reside in the most hypoxic areas in the BM suggesting that low oxygen levels might play a key role in the maintenance of HSC. However the molecular mechanisms by which HSC respond to hypoxia have not been elucidated. Cells have developed a molecular mechanism for oxygen sensing. An important mediator is the transcriptional complex hypoxia-inducible factor (HIF). At low oxygen levels, HIF is stabilized and regulates the transcription of crucial genes involved in cell proliferation, survival and differentiation. Under normoxia, HIF has a low transcriptional activity. In addition, HIF has been reported to be upregulated in certain pathological conditions such as cancer where a high expression of HIF correlates with a poor prognosis. The aim of this project is to understand the molecular mechanisms by which human HSC response to their hypoxic environment. I will address this question by studying the role of HIF in HSC. I will first concentrate on analysing the consequences that genetically manipulating HIF might have on HSC in vitro and in vivo. Secondly I will analyse whether HIF is upregulated in leukemic stem cells (LSC) and in such a case, I will finally investigate the consequences that downregulating HIF might have in the modulation of leukaemia. Defining the role of HIF in HSC and LSC will provide for the first time a molecular link between the hypoxic niche, HSC maintenance and leukaemia development in humans.
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 biological sciences cell biology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine oncology leukemia
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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-2009-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
E20 1JQ LONDON
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.