Project description
Amyloid protein-lipid aggregates roles in severe diseases
Amyloid proteins (amylin, amyloid beta, and α-synuclein) have been linked to type 2 diabetes, Alzheimer’s disease, and Parkinson’s disease, respectively. This highlights the role of lipids in membrane damage and supports the lipid-chaperone hypothesis. With the support of the Marie Skłodowska-Curie Actions programme, the LIPAGG project will investigate amyloid protein-lipid aggregates and their roles in diseases like Alzheimer’s, Parkinson’s, and type 2 diabetes. Focusing on amylin, amyloid beta, and α-synuclein, it will explore cellular toxicity, aggregation mechanisms, and interactions with lipid membranes. The project will train doctoral candidates to develop strategies to inhibit harmful aggregate formation. Overall, it aims to enhance our understanding and potential treatments for these diseases.
Objective
The LIPAGG project seeks to unravel the structural complexities of amyloid protein-lipid aggregates and investigate their role in pathological aggregation, cellular toxicity, and intercellular spread. Focusing on key human amyloid proteins—amylin (IAPP), amyloid beta (Aβ), and α-synuclein (αS)—linked to type 2 diabetes (T2D), Alzheimer's disease (AD), and Parkinson’s disease (PD), respectively, the project builds on recent discoveries made by the consortium. These findings highlight the critical role of free lipids in membrane damage through the formation of stable lipid-amyloidogenic protein complexes, leading to the lipid-chaperone hypothesis.
The project will explore unresolved mechanisms linking amyloid aggregation to cellular damage, focusing on three key aspects: 1) the toxicity of prefibrillar amyloid oligomers, 2) the interaction of amyloid proteins with lipid membranes, and 3) the pathological spread of amyloid aggregates in the brain. Guided by the lipid-chaperone hypothesis, the consortium will train fifteen Doctoral Candidates (DCs), emphasizing the pivotal role of lipids in amyloid-related diseases. The training program will include cutting-edge methods in biophysics, peptide chemistry, molecular and structural biology, and cell biology.
The scientific objectives of LIPAGG include characterizing amyloid-lipid complexes, understanding their impact on aggregation and membrane integrity, assessing their effects on cellular viability and intercellular spread, and developing chemical tools to block the formation of these complexes, offering potential therapeutic strategies. The results will have significant societal impact, enhancing our understanding of AD, PD, and T2D, including potential improvements in diagnostic and therapeutic approaches. With support of a consortium of 23 partners from 8 countries, DCs will have access to state-of-the-art instrumentation, including 1.2 GHz NMR spectrometers, single-particle cryo-EM facilities, and supercomputers.
Fields of science (EuroSciVoc)
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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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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-DN - HORIZON TMA MSCA Doctoral Networks
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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-2024-DN-01
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75794 Paris
France
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Participants (7)
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91190 Gif-Sur-Yvette
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52428 JULICH
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80539 MUNCHEN
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1165 KOBENHAVN
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95131 Catania
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87036 ARCAVACATA DI RENDE
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751 05 Uppsala
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Partners (15)
Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
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33000 Bordeaux
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40225 Dusseldorf
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37073 Gottingen
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6361 HK Nuth
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112 51 Stockholm
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70019 Triggiano
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53757 Sankt Augustin
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76275 ETTLINGEN
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2500 Valby
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2630 Taastrup
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75009 Paris
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67100 Strasbourg
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223 62 LUND
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
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86073 POITIERS
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68161 Mannheim
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
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.