Project area or title
Development and application of native ambient mass spectrometry imaging in understanding the molecular mechanisms of dementia
The aim of this PhD project is to develop and apply a new analytical imaging technique, which offers unprecedented insight at a molecular level, to interrogate molecular pathology associated with neurodegeneration, including dementia and cognitive decline. The project falls under the DTP themes of “Dementia” and “Physical Health & Mental Health Morbidity”.
Researchers in the lead supervisor’s laboratory have developed an analytical tool, native ambient mass spectrometry (NAMS), which enables detection, identification and imaging of intact proteins in their native state directly from thin tissue sections. To date, we have applied this tool to the analysis of brain tissue sections from mouse models of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterised by progressive muscle weakness and wasting, and eventually respiratory failure. These exciting results show that NAMS offers great potential beyond this specific disease for understanding neuropathology on a molecular scale.
This project will further develop the technique of NAMS and extend its application to understanding neurodegeneration and cognitive decline more broadly. Initial work will focus on the development of the technique for molecular neuropathology using brain samples from rodent models. Later work will extend NAMS to analysis of human brain and spinal cords. One of the supervisory team is Director of the Sheffield Brain Tissue Bank which holds tissue from a variety of dementia cases, including frontotemporal dementia (FTD), which has an overlap with ALS in terms of the molecular pathology. Ultimately, the aim is to understand molecular pathology in dementia and cognitive decline.
Dementia, Physical Health and Mental Health Multimorbidity
University of Birmingham