Principal Investigators

    Prof Sheena Radford


    University of Leeds

    Contact information of lead PI


    United Kingdom

    Title of project or programme

    The molecular mechanisms of structural conversion and toxicity in amyloid disease.

    Source of funding information

    The Wellcome Trust

    Total sum awarded (Euro)

    € 1,255,372

    Start date of award


    Total duration of award in years


    The project/programme is most relevant to:

    Neurodegenerative disease in general


    Research Abstract

    Despite the importance of amyloid disorders in today s population, attempts to inhibit the progress of amyloidosis have met with limited success. New therapeutic strategies require the structure, stability and dynamics of every species populated during assembly to be determined and the effects of individual species on cellular function deduced. Here we propose to combine biophysical, biochemical and cell biological approaches to address three questions that lie at the heart of our quest to understand amyloidosis at a molecular level: (i) how does molecular self-recognition occur in the earliest stages of amyloid assembly; (ii) which species nucleate fibril formation and what is the structure of higher order oligomers and amyloid fibrils; and (iii) how do amyloid fibrils and fibril-associated species exert their toxic effects? Using beta2-microglobulin as a paradigm, and embracing other assembling proteins/peptides, our aim is characterise all species possible on an as sembly landscape in order to define the entire molecular assembly pathway from monomer to fibril. In parallel, by combining different strategies we aim to derive new understandings of the origins of amyloid-associated cytotoxicity. Together the programme will provide the much-needed structural, biophysical and cellular insights required for therapeutic intervention in the years ahead.

    Lay Summary

    Further information available at:

Types: Investments > €500k
Member States: United Kingdom
Diseases: Neurodegenerative disease in general
Years: 2016
Database Categories: N/A
Database Tags: N/A

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