Axonal RNA-binding protein dysregulation in FUS-ALS pathogenesis
About the Project
Project Description:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive loss of motor neurons and degeneration of the neuromuscular system. Despite decades of research, ALS remains incurable, and the molecular mechanisms underlying selective neuronal vulnerability are still poorly understood.
Mutations in the RNA-binding protein FUS cause familial forms of ALS by promoting its mislocalisation from the nucleus to the cytoplasm, disrupting RNA processing and altering the function of other RNA-binding proteins (RBPs). As local RNA transport and translation are essential for axonal maintenance, disruption of these processes may contribute directly to pathogenesis. However, the extent to which mutant FUS remodels axonal RBP networks, and how this drives degeneration, remains unknown.
This PhD project aims to define how mutant FUS remodels RBP networks in ALS, determine whether these alterations arise from loss of normal nuclear FUS function and investigate the contribution of local toxic gain-of-function mechanisms by selectively removing mutant FUS from axons. Altogether, in this project we will identify early molecular changes that impair axonal maintenance and regeneration and providing new insights into the mechanisms driving neurodegeneration in ALS.
This PhD project offers an exciting opportunity to work at the forefront of neurodegeneration research in a highly collaborative environment. The successful candidate will be based at University College London and will benefit from collaborations with leading researchers in ALS, neurodegeneration, RNA biology, and neuronal cell biology. The student will develop expertise in stem cell models, proteomics, and advanced microscopy, while contributing to high-impact research with clear translational potential.
The candidate:
We are seeking a highly motivated individual with a strong interest in neuronal biology and the translation of fundamental research into therapeutic strategies for neurodegenerative diseases. Experience in iPSC cell culture and proteomics is desirable but not required. Applicants should hold, or expect to hold by the start date, a degree in neuroscience, biology or a related discipline.
Supervisors:
Dr Nicol Birsa and Prof. Helene Plun-Favreau.
For further information about the project, please contact Nicol Birsa (n.birsa@ucl.ac.uk) by 10th July 2026. The application deadline is 17th July 2026.
How to apply:
Please prepare a single PDF document in the following order:
- A covering letter outlining motivation, interest, and suitability for this project
- CV / resume
- Contact details for two academic referees
Apply by sending the document in an email with the subject “Brake PhD application” to: n.birsa@ucl.ac.uk
Interviews are expected to take place in early August.
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