Principal Investigators

    Sara Snogerup Linse

    Institution

    Lund University

    Contact information of lead PI

    Country

    Sweden

    Title of project or programme

    Neutron scattering studies of co-aggregation of amyloid proteins and lipids

    Source of funding information

    Swedish Research Council

    Total sum awarded (Euro)

    € 737,758

    Start date of award

    01-01-2015

    Total duration of award in years

    4

    The project/programme is most relevant to:

    Parkinson's disease & PD-related disorders

    Keywords

    Research Abstract

    The overall goal is to explore the use of isotope labels and neutron scattering to detect, quantify and obtain structural information of aggregated protein species in neurodegenerative disease. The study is focused on α-synuclein, a protein found in amyloid aggregates in Parkinson disease. α-syn monomer is more or less unfolded, but may self-assemble into aggregates, amyloid fibrils, rich in β-sheet. Many substances, including lipid membranes, affect the aggregation process. This may lead to co-aggregation of protein and lipid, influencing both the formed aggregates and the membrane. Our study is based on previous indications of co-aggregation by confocal microscopy, cryo-TEM, solid-state NMR, and reports linking α-synuclein aggregation to the interaction with lipid membranes. We will develop fluidics devices for well-defined mixing that transform reaction time to delay line length. We will use neutron scattering and reflectometry with selective deuteration of protein or lipid and different solvent contrasts to study an ongoing reaction in time-resolved mode. Our aim is to detect co-aggregates, quantify molar ratio of co-aggregated species, and to gain structural information on both transient and final aggregated species. Studies of transient on-pathway species may reveal key information on surface-catalyzed nucleation, of relevance for disease spreading. The study will open new ways to use neutrons in cutting-edge biomolecular science.

    Lay Summary

    Further information available at:

Types: Investments > €500k
Member States: Sweden
Diseases: Parkinson's disease & PD-related disorders
Years: 2016
Database Categories: N/A
Database Tags: N/A

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