Project description
The role of degradation pathways in stem cell phenotype
Haematopoietic stem cells (HSCs) have the capacity to self-renew and differentiate into all mature blood cells. Through asymmetric cell division and a complex network of regulatory events at the transcriptional, translational, epigenetic and metabolic level, they give rise to cells of divergent fates. The EU-funded Asymmetric fates project will investigate the role of autophagy and proteasomal degradation in cell fate determination in the haematopoietic system. By imaging the asymmetric inheritance of different components in HSCs, scientists will decipher the impact of degradation pathways on cell fate. The generated knowledge is expected to advance HSC applications in regenerative medicine.
Objective
The haematopoietic system relies on the potential of haematopoietic stem cells (HSCs) to self-renew and differentiate into all lineages of mature blood cells, and is a reference model to study differentiation hierarchies. Cell fate determination results from different layers of regulation, including transcriptional, translational, epigenetic, metabolic, and cell biological changes. Degradation pathways, such as autophagy and the proteasome, play mechanistically relevant roles that in principle may impact on all these layers. Indeed, catabolic degradation results in the building blocks necessary for anabolic processes, while it also preserves stemness and regenerative potential. Asymmetric cell division (ACD) has been extensively reported to contribute to maintenance of stemness by the rise of daughters with divergent fates in stem cells, including HSCs. Taken together, I postulate that degradation pathways work synergistically to give rise to the asymmetric fates observed in HSCs differentiation and can be targeted for future therapeutic use in humans. I plan to test this by 1. establishing an efficient strategy to image asymmetric inheritance of cargo by long-term ex vivo HSCs expansion, 2. verifying whether autophagosomes and proteasomes are co-inherited in HSCs mitoses, and 3. assessing the impact of cargo segregation by ACD on HSC maintenance and differentiation. I will use state-of-the-art techniques and novel murine models to assess the molecular and cell biological mechanisms of ACD modulation on HSC maintenance, relying on imaging of known and potentially novel components that are asymmetrically inherited by HSCs and able to impact their fate determination. Finally, I will further evaluate the in vivo impact of cargo inheritance on haematopoiesis by using single-cell transplantation. The knowledge derived from this project will potentially boost the development of novel regenerative medicine therapeutic approaches.
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
- medical and health sciences clinical medicine transplantation
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2019
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
OX1 2JD Oxford
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.