Single-molecule detection of the cytotoxic species in MND

Single-molecule detection of the cytotoxic species in MND

Project Code: 
2018-SPRINT-EDI1

The major pathological hallmark of Motor Neuron Disease (MND) is the accumulation of proteins containing TDP-43 (approximately 97% of cases), FUS and/or SOD1 protein (<5% of cases). Mislocalisation of TDP-43 from nucleus to cytoplasm is an early critical event in MND pathogenesis, and the aggregation of TDP-43 in the cytoplasm drives its toxicity. The application of novel biophysical methodology to track the aggregation process of TDP-43 in patient-derived cell models of MND should reveal the structure of the toxic species, and determine whether they are targets for therapy. If aggregation of TDP-43 is fundamental to pathogenesis, then single-molecule detection of aggregates would be a useful diagnostic tool, or biomarker for human disease. This project aims to achieve the following:

  1. To characterise the intracellular oligomerisation of TDP-43 in iPS derived MND models utilising super-resolution and single molecule methodology.
  2. To determine how the location and aggregation of TDP-43 in the iPS derived model causes organellar dysfunction and toxicity.
  3. To determine whether TDP-43 aggregates can be detected in sporadic ALS cerebrospinal fluid as a diagnostic tool, and within post-mortem brain tissue.

Prerequisites

This project will be ideal for a student trained in chemistry, physics or biophysics who wishes to apply physical methods to answer an important biomedical problem. No prior experience in biology is required.

 

The project is a part of SPRINT-MND/MS, a new Scotland-wide PhD scheme for research into motor neurone disease and multiple sclerosis. Projects, encompassing a wide range of topics including laboratory, clinical, and social sciences, are available at Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews Universities. This exciting initiative provides a great opportunity for budding researchers in any field related to MND or MS to join Scotland’s network of world-leading scientists and health professionals. Find more information here: http://www.edinburghneuroscience.ed.ac.uk/edneurophd/sprint-mndms-phd-programme

Additional Project Info 
Studentships are for three years and include a standard non-clinical stipend*, UK/EU fees* and an allowance for consumables and travel. The cohort of SPRINT students will also be offered opportunities to attend clinics and meet patients, undertake ‘taster’ placements in a different field, and participate in public engagement and researcher networking events. *Clinical and/or non-UK/EU applicants are eligible to apply. However, because any shortfall in stipend or fees must be met by the supervisory team, written agreement from the supervisor must accompany the application.
Secondary Host Research Centre 
Funding Status of this Project 
Deadline for Application 
Friday, 8 December, 2017
Research Area(s) 
Motor neurone disease (ALS)