PhD Studentship: Investigating RNA processing defects in Amyotrophic Lateral Sclerosis using iPSC models, genomics and imaging

The University of Exeter’s Living Systems Institute (LSI) is inviting applications for a PhD studentship funded by the Motor Neuron Disease Association to commence on 22 September 2025 or as soon as possible thereafter.  For eligible students the studentship will cover Home tuition fees plus an annual tax-free stipend of at least £20,500 for 3.5 years full-time, or pro rata for part-time study.  The student would be based in the LSI in the Faculty of Health and Life Sciences at the Streatham Campus.

Amyotrophic Lateral Sclerosis (ALS) is a deadly disease marked by the loss of motor neurons (MNs). A prevalent characteristic in ALS is the nuclear loss and cytoplasmic accumulation of the RNA-binding protein (RBP) TDP43, leading to splicing defects and cryptic exon inclusion in key genes. These splicing errors potentially disrupt MN function, yet the exact mechanism and therapeutic potential of targeting these defects remain unclear. Our research uses a novel model of TDP43 proteinopathy in human induced pluripotent stem cell-derived MNs to mimic TDP43 mislocalization without external stress. We've identified splicing errors in genes crucial for cytoskeletal integrity and neurotransmission. Our project will assess the phenotypic impacts of correcting these mis-spliced genes in MNs displaying TDP43 mislocalization, either individually or in combinations. This work will offer insights into the development of targeted therapeutics against this devastating disorder.

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