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Spotlight on liquid-liquid phase separation

- News, Biology Health, Soft matter, General news

The latest ‘Spotlight’ meeting of the Partnership in Structural Biology (PSB) brought together researchers from across the EPN campus and beyond for a morning of engaging presentations and discussions dedicated to liquid–liquid phase separation (LLPS). The ensemble of the contributions highlighted the relevance of LLPS across diverse contexts, in particular in addressing some of humankind’s core challenges related to health, disease and the environment.

LLPS is a process where two or more liquid phases form from a homogeneous solution, typically in response to changes in temperature, concentration or other factors. In living organisms, LLPS refers to the formation of membrane-less condensates (cellular 'compartments'). This mechanism regulates essential cellular processes and can be linked to several diseases.

This fast-growing field of research was under the spotlight in the meeting organised by the Partnership in Structural Biology (PSB) at the EPN campus on 18 September 2025. 

ILL Science Director Jacques Jestin opened the event, outlining how the new ILL Science Strategy will foster research in the field through the creation of a Science Hub on LLPS focused on problems relevant to human health and pathology. The Hub will consolidate internal expertise and strengthen collaborations with the Institute of Structural Biology (IBS) and the European Molecular Biology Laboratory (EMBL). 

Researchers from the ILL, IBS, CEA, Imperial College London, and the University of Tübingen shared their contributions to the field, revealing LLPS phenomena across a diverse range of systems and with a wide range of methods. 

 

Proteins such as α-synuclein and myelin basic protein (MBP) are known to exhibit LLPS. The formation of amyloid fibrils is associated with neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.  Rebecca Thrush from Imperial College London discussed the role of surface wetting as a determinant of condensate maturation, investigating how the balance between protein–protein and protein–condensate interactions influences aggregation rates and wettability in α-synuclein condensates. 

Giorgio Schirò of IBS demonstrated the suitability of neutrons as a probe to investigate proteins connected to neurodegenerative diseases, presenting quasi-elastic neutron scattering studies on α-synuclein and MBP—revealing changes in hydration water dynamics upon fibril formation and enabling real-time observation of aggregation through fixed window scans. He outlined a roadmap from characterizing fibril formation of the τ-protein in solution to understanding it under LLPS conditions. 

Martin Blackledge, also from IBS, combined NMR spectroscopy and molecular dynamics simulations to investigate the behaviour of intrinsically disordered proteins under LLPS. He highlighted LLPS phenomena as part of the measles virus replication machinery. In addition, he showed how the fiber- and hydrogel-forming capacity of tardigrade proteins may underlie the remarkable resistance of these organisms to environmental stress. 

After a lively coffee break with engaged discussions, the meeting continued with Frank Schreiber from the University of Tübingen, who presented his research on LLPS phenomena induced by “mildly exotic” charges, followed by Marc Jasmin’s (IBS) insights into LLPS mechanisms in the context of the rabies disease. Finally, Chloé Zubieta (CEA) presented how the protein ELF3 represses plant elongation growth and flowering at low temperatures and demonstrated how structural modification enables temperature regulation.


The Partnership for Structural Biology (PSB) is a collaborative research initiative bringing together several major European research institutes located on the European Photon and Neutron (EPN) campus in Grenoble to advance the field of structural biology, enabling researchers to access a comprehensive range of cutting-edge techniques and instrumentation. 


Acknowledgements: based on an original text by Theresa Bosserhoff