| Title | Identifying genetic factors that protect against neurofibrillary tangles pathologies in Alzheimer’s disease |
|---|---|
| Supervisor | Ben Pickard |
| Research Area | Cellular Basis of Disease: neurodegeneration, cell biology, molecular genetics |
| Description | Alzheimer’s disease is a common and devastating neurodegenerative disease of later life. It has profound effects on the diagnosed individual, their family and carers, and, more widely, healthcare provision. Current medications can slow symptom progression but do not tackle the underlying causes. Twin aetiologies of beta-amyloid protein production and accumulation as plaques, and the hyperphosphorylation and inactivation of microtubule-associated protein tau seem to drive the pathology; resulting in widespread inflammatory processes, and eventual catastrophic neuronal loss. In previous work, we have applied a cell-based genetic screen, called a ‘gene trap’, to identify gene mutations that confer protection against, or susceptibility to amyloid toxicity. The identified genes have provided new insights into pathways and processes to explore in the future (see submitted publication and additional PhD project). However, they represent only half of the pathological picture. The project proposed here will involve the student developing cell models and cellular assays to examine the aberrant phosphorylation and inactivation of the tau protein in order to carry out a valid cellular genetic screen for this aspect of Alzheimer’s neurodegeneration. The student would be looking for and validating the involvement of novel genes and processes that might be targets for future treatment. In this way, the student will be driving an aspect of disease therapy that has, so far, been relatively underexplored. |
| Techniques Used | Training and supervision will be provided on all aspects of the project – from cell culture, molecular biology, and microscopy, through to molecular genetics/high-throughput sequencing. |
| References | Yap et al., Functional gene trap mutagenesis screen for genes and potential signalling pathways meditating amyloid-β-induced NLRP1 inflammasome-mediated neuronal death (submitted – available upon request). Congdon EE, Sigurdsson EM. Tau-targeting therapies for Alzheimer disease. Nat Rev Neurol. 2018;14(7):399–415. doi:10.1038/s41582-018-0013-z |
| Conditions | Applicants should possess or be about to obtain a 1st class or 2:1 Honours degree or equivalent in a relevant discipline in addition to receipt of satisfactory references and an IELTS score of 6.5 where appropriate. Some practical lab experience. |
| Bench Fee | Running costs of £10000 p.a. will be associated with this project in addition to University tuition fees. |
| Suitable For | Most suited to those with a UG/PGT degree that includes modules on biology/genetics. |
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