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Identification of phase separating proteins associated with human disease

Nature Reviews Molecular Cell Biology volume 25, page 5 (2024)Cite this article

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Protein phase separation (PPS) is increasingly recognised to be of central importance in cell biology. Along with mounting evidence for the role of PPS in core biological processes, there is growing interest in the exploitation of this phenomenon for pharmacological interventions. However, the nature of the link between PPS and human disease remains poorly understood. Thus, methods to quantify the association of PPS with diseases, and to identify and validate protein targets for drug discovery are urgently required.

Towards this goal, in a collaboration with Insilico Medicine, we have proposed a pipeline for the identification and characterization of protein targets whose phase separation is altered in disease. Our approach opens an avenue to uncover previously unknown molecular mechanisms of disease. Based on this understanding, one can then develop preclinical models in which the phase separating behaviour of the protein targets could be pharmacologically modulated.

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References

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  • Lim, C. M. et al. Multiomic prediction of therapeutic targets for human diseases associated with protein phase separation. Proc. Natl Acad. Sci. USA 120, e2300215120 (2023)

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Acknowledgements

The authors thank M. Vendruscolo and InSilico Medicine for their guidance, support and insights that were key for the completion of the work described in this article.

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  1. Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK

    Christine M. Lim & Alicia González Díaz

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  1. Christine M. Lim
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  2. Alicia González Díaz
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The authors contributed equally to all aspects of the article.

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Correspondence to Christine M. Lim or Alicia González Díaz.

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Competing interests

The PhD of C.M.L. is partially funded by Insilico Medicine.

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Lim, C.M., González Díaz, A. Identification of phase separating proteins associated with human disease. Nat Rev Mol Cell Biol 25, 5 (2024). https://doi.org/10.1038/s41580-023-00672-1

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  • DOI: https://doi.org/10.1038/s41580-023-00672-1

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