Project description
Insight into selective protein secretion
Cells transport proteins to their surface or secrete them to the extracellular space to communicate with other cells and maintain tissue integrity. This process begins in the endoplasmic reticulum (ER), where only correctly folded proteins are packaged into vesicles for further transport. However, it remains unclear how these vesicles select the proteins to be transported. With the support of the Marie Skłodowska-Curie Actions programme, the PACK-COP project aims to elucidate the mechanism behind this selectivity. Researchers will focus on a specific family of cargo receptors and their interactions with protein cargo. The outcome of this project can guide future therapeutic strategies for diseases including cancer and neurodegenerative disorders that involve targeting protein trafficking.
Objective
Protein secretion is an essential cellular process that delivers many diverse proteins to the extracellular environment or cell surface. This process contributes to many aspects of cellular function, including nutrient uptake, cellular communication and tissue integrity. Secretion starts with secretory protein biogenesis and folding in the endoplasmic reticulum (ER) followed by their export from the ER and transport to the Golgi apparatus via COPII-coated vesicles, to finally reach their final destinations. These vesicles play a pivotal role in quality control of secretion by selectively packaging cargo proteins that are fully folded and transport competent. Defects in this process can lead to diseases such as cancer and neurodegenerative disorders. However, the molecular mechanisms governing selectivity in vesicular trafficking remain poorly understood.
PACK-COP will reveal how a specific family of cargo receptors, Erv14/CNIH, drives the selectivity of secretion across a diverse range of clients. The molecular mechanism underlying this selectivity into nascent vesicles will be dissected using a combination of yeast and human model systems. In yeast, PACK-COP will use mutagenesis and specific cross-linking approaches to discover protein-protein interaction interfaces that drive multiple known cargo proteins into COPII vesicles. These insights will be directly applied to human cells to map the client landscape that uses CNIH1 for ER export, and test specific functional domains based on the yeast discoveries.
The innovative combination of both models, coupled with cutting-edge techniques, will enable PACK-COP to map Erv14 specific amino acids required for the ER export of critical cell-surface proteins. This knowledge could enable screening for inhibitors that block these interactions, potentially reducing the release of specific proteins to the cell surface, a strategy with significant therapeutic potential for disease associated to defects in secretion pathways.
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
- medical and health sciences clinical medicine oncology
You need to log in or register to use this function
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
See all projects funded under this funding scheme
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-2024-PF-01
See all projects funded under this callCoordinator
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.
DD1 4HN Dundee
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.