Objective
The capacity of the cell to maintain protein quality and function diminishes upon aging and disease. Genetic mutations may result in protein malfunction or structural defects due to an alternation of an essential amino acid. The cell has evolved many mechanisms to handle misfolded proteins; some proteins are refolded by molecular chaperones while others are targeted for degradation by the ubiquitin proteasome system and yet others are sequestered in deposits at a specific cellular location. How cells make decisions on a specific protein destination is only hardly understood and progress in this field is slow due to the lack of useful chemical and biological tools.
In this proposal I will address this question by using a methodology that allows visualization of the cellular response towards an unfolded protein of which the physical properties are well known. The protein is genetically incorporated and correct folding is initially maintained by a small molecule ligand. The proteins are designed to vary in hydrophobicity and stability of the core structure. Unfolding of the protein is induced by depletion of the ligand after which the cellular response can be monitored. With the help of molecular tools it is possible to label interacting proteins that recognize the pool of unfolded proteins at specific stages of the quality control pathway. In addition, current mass spectrometry technologies allow identification of posttranslational modifications which are important for defining the final destination of the unfolded protein. The technology is further elaborated on protein aggregates that play a role in many neurodegenerative diseases.
Information that arises from this study gives novel insights in the cellular dynamics and recognition of misfolded proteins. Understanding these processes will help in the development of novel diagnostics and therapeutics for diseases that are related to misfolded proteins or a defect in the cellular protein quality control machinery.
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 biological sciences genetics mutation
- natural sciences chemical sciences organic chemistry amines
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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.
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.
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.
FP7-PEOPLE-2013-CIG
See other projects for this call
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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
6525 XZ Nijmegen
Netherlands
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.