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Proteins can self-organize into a remarkable diversity of higher-order structures, ranging from dynamic biomolecular condensates to highly ordered amyloid assemblies. These transitions provide cells with powerful mechanisms to spatially and temporally regulate biological functions and are central to cellular organization. However, when misregulated, the same processes can contribute to a wide range of human diseases, including neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.
In this talk, I will explore protein self-organization across different biological scales, from in silico predictions of protein self-assembly propensity and in vitro reconstitution with purified proteins to the study of these processes in living cells. Drawing on examples from cellular metabolism, stress responses, and immunity, I will discuss how integrating these different scales can uncover the biophysical principles governing transitions between soluble, condensed, and amyloid states, how cells harness these transitions to regulate function, and how their dysregulation may contribute to ageing and disease. Together, these findings highlight protein self-organization as a unifying principle connecting molecular interactions to cellular and organismal function.
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