Currently, no treatments are available to halt the progression of dementia-causing illnesses, including Alzheimer’s disease (AD), Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB). Such disorders are pathologically characterised as ‘proteinopathies’ and are caused by the misfolding and aggregation of proteins. The molecular basis of these disorders remains unknown. However, the rates of turnover, aggregation and degradation of such proteins are known to be modulated by post-translational modifications (PTMs), including phosphorylation. Thus, examining such modifications may uncover the mechanisms leading to neurodegeneration and perhaps identify novel intervention strategies in dementia.
The aim of this PhD project is to identify key PTMs associated with the phosphoproteome in the pathological hallmarks of AD and PDD/DLB. Phosphorylation patterns will firstly be identified in post-mortem tissue using Raman microscopy, immunohistochemistry, liquid chromatography mass spectrometry (LC-MS/MS), enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. Characterisation of functional changes associated with the expression of phosphorylated proteins of interest will be assessed in cell models, and a variety of assays will report on cellular homeostatic and viability processes.
The project will form part of a wider collaboration of groups at Newcastle and Göttingen University on the role PTMs in neurodegenerative disease. The successful applicant will have the opportunity to meet regularly and work closely with these teams.
Applicants should use the links provided in each topic or project area to the Research Centres and Research Groups identified, or to the named supervisors for each project, to ensure that their application and proposal fits with the research interests and topics defined in the studentships offered.
The studentship will cover tuition fees and provide an annual tax-free stipend of £15,000 for three years, subject to satisfactory progress. Applications are welcome from strong UK, EU and International students.