|Location:||Newcastle upon Tyne|
|Salary:||£33,966 to £37,099 per annum|
|Placed On:||18th September 2023|
|Closes:||25th October 2023|
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Modelling human motor neurone disease/fronto-temporal dementia (MND/FTD) in cortical organotypic slice cultures.
This position offers an exciting opportunity for a Research Associate to work on a new project funded by the Motor Neurone Disease Association. Motor neurone disease and fronto-temporal dementia (MND/FTD) are characterised by the accumulation of the protein transactive response DNA-binding protein (TDP-43), in brain cells. However, how the increased levels of TDP-43 cause neurodegeneration is still unclear. This project will involve the development of a novel translational slice culture platform which will use viral transduction approaches to express genes linked to MND/|FTD in neurons in cortical tissue obtained from mouse, non-human primates, and humans. Using this mouse-to-man model platform we aim to gain important new insights into the early pathological changes associated with abnormal TDP-43 expression.
This project will focus on extending our existing models of adult mouse and human organotypic cultures to optimise viral transduction methods using both wild type and mutant forms of TDP-43 to model MND/FTD. After optimisation of the viral constructs in slice cultures we want to understand the impact of abnormal expression of TDP-43 on cellular and network activity. We will study cell-to-cell spread of pathology and seek to understand the early changes evoked by abnormal pathology on cellular and network function. Studies will include detailed immunohistochemistry to assess phosphorylation of TDP-43 and changes in markers of oxidative stress, mitochondrial function and neuroinflammation. We will also use electrophysiological recording approaches, including whole-cell patch-clamp, calcium imaging and multichannel recordings to assess how TDP-43 associated pathology alters neuronal and network properties. Our goal will be to develop an organotypic model platform that will improve our understanding of the early neurodegenerative changes associated with MND/FTD. Ultimately this platform could then be used to assess novel therapeutics approaches that might benefit patients with MND/FTD.
This post is full time, fixed term for a period of 2 YEARS- 1st January 2024 to 31st December 2025
For informal enquiries contact: Dr. Fiona LeBeau (Fiona.firstname.lastname@example.org) or Prof. Mark Baker (email@example.com); Prof Stuart Baker (firstname.lastname@example.org) or Dr. Faye McLeod (email@example.com).
Find out more about the Faculty of Medical Sciences here: https://www.ncl.ac.uk/medical-sciences/
Find out more about our Research Institutes here: https://www.ncl.ac.uk/medical-sciences/research/institutes/
As part of our commitment to career development for research colleagues, the University has developed 3 levels of research role profiles. These profiles set out firstly the generic competences and responsibilities expected of role holders at each level and secondly the general qualifications and experiences needed for entry at a particular level.
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