Project description
Extra chromosomes may be linked to kidney repair
The body is continually undergoing growth and repair, with new cells forming on a regular basis through mitosis. During mitosis, the genetic material is duplicated and the cell divides with each of two daughter cells receiving a complete copy of every chromosome. The endocycle is a normal variant of the cell cycle where cells replicate their genomes without dividing. Widespread in protozoa, plants and animals, its role in repair of mammalian tissues is unclear. ROAR is exploring the potential role of endocyles in recovery of renal function after acute kidney injury. Insight may also help reduce occurrence of chronic kidney disease following recovery from acute kidney injury.
Objective
Acute kidney injury (AKI) is a global public health concern which results in 1.7 million deaths per year. If not lethal in the acute phase, AKI is considered reversible as suggested by recovery of renal function. However, even mild AKI episodes carry substantial risk of developing subsequent chronic kidney disease (CKD). The pathophysiological basis for this phenomenon remains unclear.
Injury and death of tubular cells are recognized as the main factors in the pathogenesis of AKI and functional recovery from AKI was traditionally attributed to the regenerative capacity of tubular epithelial cells (TECs) which are believed to re-enter the cell cycle and repair the damage. Nevertheless, my preliminary data provide evidence that an endocycle-mediated response of remnant TECs may represent a critical mechanism of response to AKI.
Endocycles are cell cycle variants consisting of G and S phases alone that repeatedly proceed without cytokinesis and its role in repair of mammalian tissues is mostly unknown and totally unexplored in the kidney.
This proposal will be structured into 3 distinct objectives to address: 1. The physiologic relevance of endocycle for kidney function recovery after AKI 2. The role of endocycle in the progression of AKI to CKD; 3. The mechanism by which YAP1 drives endocycle and contributes to CKD development. To this end I will use lineage tracing techniques based on the FUCCI2aR reporter applied in different transgenic animal models of AKI, together with in vitro experiments in human primary cultures of renal tubular cells.
Collectively, the outcomes of this proposal are expected to provide an entirely novel view of the kidney’s response to AKI, to further our understanding of the processes that drive CKD following AKI, as well as to describe for the first time endocycle as a critical response mechanism to tissue injury in the mammalian kidney.
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 health sciences public health
- medical and health sciences clinical medicine nephrology kidney diseases
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Programme(s)
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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
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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)
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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.
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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-EF-RI - RI – Reintegration panel
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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50121 Florence
Italy
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