Open AccessKinetic analysis reveals that independent nucleation events determine the progression of polyglutamine aggregation in C. elegans
Author(s) -
Tessa Sinnige,
Georg Meisl,
Thomas C. T. Michaels,
Michele Vendruscolo,
Tuomas P. J. Knowles,
Richard I. Morimoto
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2021888118
Subject(s) - protein aggregation , nucleation , caenorhabditis elegans , biophysics , biology , amyloid (mycology) , in vitro , chemistry , biological system , computational biology , microbiology and biotechnology , biochemistry , gene , botany , organic chemistry
Significance Diseases associated with amyloid formation affect millions of people worldwide. Great progress has been made to understand the process of amyloid formation in test tube reactions, but it has so far remained unclear if the same biophysical principles also dominate in living cells and organisms. Here, we use the nematodeC. elegans to demonstrate that we can apply kinetic modeling approaches to quantitatively analyze the process of protein aggregation in a living animal. The mathematical models that we develop are not restricted to this system and are applicable to other disease-associated proteins and animal models. The ability to quantitatively understand aggregation mechanisms in living organisms will be critical to advance our understanding of human disease and to design therapeutic strategies.