Engineering Living Matter

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Engineering Living Matter

1. New Tools to Study Phase Separation in Living Cells

Biomolecular condensates formed by intracellular phase separation organize essential cellular processes, from gene regulation to metabolism. While phase separation is now recognized as a key organizing principle, the rules governing condensate composition, dynamics, and function remain poorly understood. To address this, we develop engineered artificial scaffolds that form phase-separated condensates directly in living cells (Cochard et al., EMBO J. 2023; Biophys. J. 2022). This bottom-up approach enables precise control of condensate properties within the native cellular environment, allowing us to engineer new cellular functions and model pathological condensates linked to aging and disease.

2. Harnessing Biochemical Processes with Synthetic Condensates

Cellular compartmentalization relies on dynamic exchange between organelles, yet existing perturbation methods lack specificity and control. We developed ControLD, a strategy to physically isolate lipid droplets—key organelles in energy storage and stress protection (Amari et al., Nat. Chem. Biol. 2025). ControLD uses engineered phase-separating proteins to form a reversible meshwork on lipid droplets, selectively blocking their metabolism and enabling direct interrogation of organelle communication.

3. Biophysics of Proteinopathies in Neurodegeneration and Cancer

Many neurodegenerative diseases arise from the conversion of soluble proteins into pathological aggregates, including α-synuclein, TAU, and TDP-43. How these aggregates drive cellular dysfunction remains unclear. We develop cellular models of disease-relevant condensates and aggregation. Recently, we showed that spreading α-synuclein aggregates convert liquid α-synuclein condensates into amyloids (Piroska et al., 2025), providing a controlled system to study pathogenic aggregation mechanisms.

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