ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule Function.
- Submitting institution
-
University of Cambridge
- Unit of assessment
- 12 - Engineering
- Output identifier
- 7429
- Type
- D - Journal article
- DOI
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10.1016/j.neuron.2015.10.030
- Title of journal
- Neuron
- Article number
- -
- First page
- 678
- Volume
- 88
- Issue
- 4
- ISSN
- 1097-4199
- Open access status
- Out of scope for open access requirements
- Month of publication
- November
- Year of publication
- 2015
- URL
-
-
- Supplementary information
-
-
- Request cross-referral to
- -
- Output has been delayed by COVID-19
- No
- COVID-19 affected output statement
- -
- Forensic science
- No
- Criminology
- No
- Interdisciplinary
- No
- Number of additional authors
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29
- Research group(s)
-
-
- Proposed double-weighted
- No
- Reserve for an output with double weighting
- No
- Additional information
- We prove that a protein called FUS can reversibly phase separate into hydrogels in neurons with impairment leading to toxicity. We show that FUS hydrogels trap RNA and this alters the cell's capacity for protein synthesis, providing a possible model for the onset of toxicity in a disease called ALS. We use a range of biophysical and biological tools in this interdisciplinary collaboration. Publication of the work led to a 3.1M collaborative grant from the Wellcome Trust awarded to the lead authors (https://wellcome.ac.uk/funding/people-and-projects/grants-awarded/liquid-droplets-hydrogels-protein-phase-transition) and a high impact follow on publication by the consortium in the Journal cell (https://doi.org/10.1016/j.cell.2018.03.056)
- Author contribution statement
- -
- Non-English
- No
- English abstract
- -
