Project description
A closer look at what happens when organelles get up close and personal
Mammalian cells are loaded with membrane-bound organelles that compartmentalise their work according to various cellular functions. Just like in a real factory, different 'departments' sometimes work together. Execution of biological processes such as phospholipid biosynthesis and calcium signalling require two organelles to be close but not touching. Perhaps the best known interorganelle contact points are the mitochondria–endoplasmic reticulum contact sites (MERCs). These dynamic structures change in response to the metabolic state of the cell, with the contact surface area and gap width being important structural elements. The multifunctional roles of MERCs are largely unknown, but recent evidence suggests their implication in disease as well as health with a link to lipid metabolism in Alzheimer's disease. The EU-funded MERCURY project is investigating the regulation of MERC dynamics by small molecules through the screening of bioactive molecules and the identification of their protein targets.
Objective
Mitochondria and Endoplasmic Reticulum (ER) Contact sites (MERCs) are points in which the surfaces of the two organelles run in parallel. MERCs gained attention recently due to their fundamental contribution to several cell processes, such as Ca2+ and lipid homeostasis, mitochondrial fission, and apoptosis. To execute and regulate these processes, MERCs must be dynamic and react to the needs and metabolic state of the cell. Interestingly, the organelles stay separated by a narrow cleft, usually 10-50 nm apart. The width of the MERCs gap and its size (i.e. area of a membrane involved in the contacts) are the critical parameters that determine their cellular functions. Despite the literature on MERCs has grown considerably, the precise molecular structure and role of MERCs are poorly defined.
In the proposed project I will investigate the regulation of MERCs plasticity by small molecule compounds. Using a high-content phenotypic screening approach, based on a FRET mitochondria-ER proximity probe, I will identify the compounds affecting MERCs structure. These bioactive hits will be validated through biochemical, confocal and electron microscopy assays. Moreover, I will search for the protein target of the hit molecule using the methodology developed during my PhD. Finally, I will evaluate the capability of the identified hit molecules to act as therapeutic lead compounds for pathological conditions by testing the identified molecules on cells with defective MERCs. Therefore, this project will open new research paths related to both MERCs structure and function.
I will obtain deep knowledge of mitochondrial biology and high content screening, which will complement my current expertise obtained during PhD. Besides, I will develop transferable skills needed to successfully accomplish the proposed project. The project also brings the benefits to the European Research Area, since it builds international collaboration and transfers knowledge between two research areas/teams.
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 biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine physiology homeostasis
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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.
35122 PADOVA
Italy
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.