Project description
Identifying the molecular mechanisms of intracellular density homeostasis
Cells are often referred to as factories. Macromolecules are shuttled among ‘departments’ as well as into and out of the cells, as they are processed, or to carry signals. The cytoplasm is packed with macromolecules close to the physical limit, potentially creating ‘traffic jams’ and obstructing cellular processes and functions. The overall intracellular concentration of macromolecules is relatively constant within a cell type, but it varies during important physiological transitions. It is not clear how this is regulated. With the support of the Marie Skłodowska-Curie Actions programme, the CrowdControl project aims to identify the molecular mechanisms underlying intracellular density homeostasis with targeted genetic manipulations and quantitative live cell imaging.
Objective
The cytoplasm is filled with an extremely high concentration of macromolecules that is close to the maximal physical limit. Such a tight packing of macromolecules gives rise to a crowding effect that influences chemical reactions and protein dynamics. Changes in crowding levels are therefore predicted to have profound consequences on cell function. It is therefore not surprising that the overall intracellular concentration of macromolecules is very constant within a cell type, but it varies during important physiological transitions such as cell division, differentiation, and senescence. How crowding is regulated is poorly understood but feedback coupling between intracellular density and cell growth has been observed in multiple systems. The CrowdControl project will combine two unbiased screening approaches with targeted genetic manipulations and quantitative live cell imaging to identify the molecular mechanism underlying intracellular density homeostasis. Specifically, we will: (i) identify proteins that can sense intracellular density changes by performing structure sensitive mass spectrometry in cells with different levels of macromolecular crowding; (ii) perform a CRISPR-knockout screen to identify mutations that affect density homeostasis; and (iii) use quantitative live cell microscopy to investigate whether proteins identified in (i) and (ii) affect feedback coupling between intracellular density and cell growth.
A better understanding of intracellular density regulation will allow the development of precise tools to alter crowding and identification of crowding sensitive proteins will give insight into what processes may respond to density changes. The results of this project will therefore be key to understanding how cells finely tune their intracellular density levels, but in addition they will also lay the basis for understanding how density changes affect cell function during the cell cycle, senescence, and differentiation.
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
- natural sciences biological sciences genetics mutation
- 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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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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.
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships
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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) HORIZON-MSCA-2023-PF-01
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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.
75231 Paris
France
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