Unveiling Early Motor Neurone Disease Biomarkers: Insights from Neuromuscular Junction Dynamics

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that leads to the degeneration of motor neurons (MNs) in the brain and spinal cord. ALS is the most common motor neuron disease (MND), and unfortunately, there are currently no effective therapies for its treatment. A pressing challenge in ALS research is the identification of early biomarkers for timely detection. Additionally, a deeper understanding of the changes occurring in neurodegenerative tissues during early stages could facilitate the development of novel therapeutic strategies.

Recent investigations have revealed that one of the earliest signs during the preclinical stage of ALS involves alterations in the neuromuscular junction (NMJ). The NMJ, the synapse connecting motor neurons and muscle fibres, plays a crucial role in motor control, and its disruption is often associated with the presence of axon defects or axonopathies. These findings challenge the previously held belief that ALS initiates in the brain.

This project aims to understand the link between molecular signalling, maintenance of NMJ and neurodegeneration. For this, we will use a combination of light and chemical imaging, behavioural and molecular techniques, including CRISPR/Cas9 genome editing, transcriptomic, and proteomic approaches.

The outcomes of this project will pave the way for the discovery of novel early biomarkers for ALS, offering the potential for early intervention and enhanced treatment strategies.

This project will involve the application of state-of-the-art imaging and molecular techniques, including CRISPR/Cas9 genome editing, as well as transcriptomic and proteomic approaches. Importantly, during this programme you will be trained in the use of zebrafish in biomedical research.

During this project, the candidate will have the opportunity to:

●     Implement state-of-the-art genome editing techniques, specifically CRISPR/Cas9, as part of this project to advance our understanding of molecular mechanisms in neural regeneration.

●     Develop skills in molecular and cellular analysis techniques, with a focus on genomic and transcriptomic analysis. This encompasses advanced chemical and light imaging techniques, as well as gene expression analysis.

●     Gain hands-on training in utilising cellular models and zebrafish, an emerging vertebrate model for studying disease, development, and regeneration.

●     Contribute to new regeneration strategies as part of the project’s goals. The outcomes of this project may pave the way for innovative approaches to address trauma in the human CNS.

General admissions criteria

You’ll need a good first degree from an internationally recognised university (minimum upper second class or equivalent, depending on your chosen course) or a Master’s degree in Biomedical or Biological Sciences or a related area. In exceptional cases, we may consider equivalent professional experience and/or Qualifications. English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

How to Apply

Please forward your motivation letter and CV directly to Dr. Jordi Cayuso (jordi.cayuso@port.ac.uk).

Visit our website for additional information on our research aims: https://www.port.ac.uk/about-us/structure-and-governance/our-people/our-staff/jordi-cayuso-mas

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