Project description
Structural analysis of the protein fibrils in the Huntington’s disease brain
The formation of protein fibrils in the brain is the most obvious sign of neurodegenerative diseases. The severity of Huntington’s disease (HD) symptoms and the onset age strongly correlate with an abnormally high number of glutamines in the huntingtin protein of affected individuals. Funded by the Marie Skłodowska-Curie Actions programme, the HUNTING-BrainFibrils project aims to obtain the atomic structures of soluble and insoluble fibrils extracted from the brains of patients with huntingtin gene mutations and map their in-situ interactions. The research will be conducted by an interdisciplinary research group, consisting of experts in HD pathology, structural biology, and interactomics. It will utilise state-of-the-art cryogenic electron microscopy, mass spectrometry-based proteomics, and immunological analysis.
Objective
The formation of protein fibrils in the brain is the most representative feature of neurodegenerative diseases. A detailed description of their structure and composition is essential to design new therapeutic approaches that allow patients to increase their life expectancy and quality of life. In Huntington’s disease (HD), the severity of the symptoms and the age of onset is strongly dependent on the number of glutamines above the threshold carried by the huntingtin protein of patients affected with this disorder. The two main objectives of this project are 1) to obtain atomic models of soluble and insoluble fibrils extracted directly from the brain tissues of individuals carrying extreme and moderate CAG repeats in the HTT gene and 2) mapping their in-situ interactions. Our approach will include state-of-the-art cryogenic electron microscopy, mass spectrometry-based proteomics and immunology. It will count on the participation of an interdisciplinary research group, comprising experts in HD pathology, structural biology and interactomics. The host institution counts with advanced facilities in image data analysis, cryo-EM and high-throughput proteomics that will be fully available. The host lab is an internationally recognised group that has more than 20 years of experience in carrying research focused on the molecular causes of HD in cell and animal models. It also has a strong background in mapping the interactions of the proteins that cause neurodegeneration in brain tissues. The host lab will take advantage of my expertise in assessing and validating protein-protein interactions through biochemical and biophysical methods. My visibility as a researcher will be greatly benefited by the extensive collaboration network of the host lab. The training and skills acquired during the execution of this project will expand and consolidate my research career and bring it to a very competitive point for taking a leading role as an independent researcher.
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 neurobiology
- natural sciences computer and information sciences data science
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences molecular biology structural biology
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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)
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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.
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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
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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13125 Berlin
Germany
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