Project description
Microbial trigger of Parkinson’s disease
Parkinson’s disease (PD) is a neurodegenerative disorder characterised by a pathological aggregation of alpha-synuclein. Emerging evidence indicates a link between the gut microbiota and alpha synuclein. With the support of the Marie Skłodowska-Curie Actions programme, the MICROSYN project aims to investigate how biofilm-associated proteins (Baps) secreted by bacteria can trigger alpha-synuclein aggregation. Researchers will focus on BapSa from Staphylococcus aureus and Esp from Enterococcus faecalis and uncover their fibrillar structure. Using atomic force microscopy, they will study the interactions of these proteins with alpha-synuclein. Results could pave the way towards new therapeutic strategies for PD, as well as antibiofilm agents to tackle antimicrobial resistance.
Objective
The global rise in Parkinson’s disease (PD) and other neurodegenerative disorders is becoming an important public health concern in the European Union and worldwide. Recent discoveries have revealed a direct connection between biofilm-associated proteins (Baps) from the human microbiota and alpha-synuclein (alpha-Syn) aggregation - a pathological hallmark of PD - supporting the hypothesis that the gastrointestinal tract plays a role in the pathogenesis of neurodegenerative diseases. The MICROSYN project aims to investigate the molecular mechanisms behind the impact of Bap proteins - BapSa from Staphylococcus aureus and Esp from Enterococcus faecalis - on the aberrant assembly of alpha-Syn. Currently, structural models of BapSa and Esp amyloid fibrils and the intermolecular interactions during the templating of alpha-Syn aggregation are unknown.
Utilizing the state-of-the art techniques magic angle spinning solid-state nuclear magnetic resonance and atomic force microscopy, this project will provide atomic-level information on Bap and Esp amyloid fibril structure and dynamics, reveal conformational changes upon cross-seeding with alpha-Syn, and offer valuable insights into the fibril architectures at the mesoscopic scale. This will be achieved through the expertise of Dr. Álvarez-Mena in the biochemistry and molecular biology of bacterial amyloids, combined with the host lab know-how in solid-state NMR, AFM and complementary physico-chemical techniques, supported by the cutting-edge facilities of the host institution.
Understanding the interaction between microbiota-derived BapSa/Esp and human alpha-Syn will offer new therapeutic avenues for combating PD, while insights into the structures of BapSa and Esp fibrils will aid in developing antimicrobial and antibiofilm agents to tackle antibiotic resistance. Thus, the MICROSYN project will support EU health priorities by fostering innovation in disease prevention and treatment.
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
- medical and health sciences basic medicine neurology parkinson
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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)
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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
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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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(opens in new window) HORIZON-MSCA-2024-PF-01
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75794 PARIS
France
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