Project description
Insight into key mitochondrial enzymes
Polynucleotide phosphorylase (PNPase) is an evolutionary conserved enzyme with a key role in RNA degradation and homeostasis. Recent evidence on the bacterial homologue shows that PNPase may also serve as a chaperone for regulatory RNA molecules. The aim of the EU-funded MitoPNP project is to study the functions and biological role of the human PNPase. Given that the enzyme localises in the intermembrane space of mitochondria, researchers speculate that it may be involved in mitochondrial RNA transport. Results will provide fundamental knowledge on mitochondrial biology and help understand the aetiology of PNPase-related disorders.
Objective
Throughout the eukaryotic lineages, mitochondria are essential organelles that provide cellular metabolic power through oxidative phosphorylation. In the mitochondrial intermembrane space resides an exoribonuclease highly conserved in the course of evolution: PNPase. Although the activity of this enzyme has been extensively studied, its function in this compartment is poorly understood. A clue to one of its potential functions has been provided by my recent findings on the bacterial PNPase, which I discovered to switch activity from an RNA degradation mode to a stabilising mode that chaperones regulatory RNAs. As the human and bacterial enzymes are homologues, it is possible that human PNPase (hPNPase) could have a dual mode of action as well, and could participate in regulatory processes or RNA cargo transport once trapped in a non-degradative assembly.
My research will address what functions are played by hPNPase present in the intermembrane space of the human mitochondria. I will characterise the full-length enzyme and its capacity to bind substrates in the degradative and non-degradative modes. In order to achieve these objectives, I will elucidate the structure-function relationship of hPNPase by cryo-electron microscopy complemented with biochemical and biophysical assays. The results will illuminate the biological roles of PNPase in human cells including its potential contributions to mitochondrial RNA trafficking. This interdisciplinary project with potential applications in human health will apply recent breakthrough advancements in cryo-EM in order to investigate the molecular basis of an intricate biological system to advance the understanding of mitochondria biology. The research effort will foster the career development of a talented researcher and contribute to the academic and research excellence in Poland by strengthening the expertise in cryo-EM, a method currently revolutionising structural biology, at the University of Warsaw.
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 physical sciences optics microscopy
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
- natural sciences biological sciences molecular biology structural biology
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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.4. - SPREADING EXCELLENCE AND WIDENING PARTICIPATION
MAIN PROGRAMME
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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.
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-WF-2018-2020
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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.
00-927 WARSZAWA
Poland
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.