The impact of altered tau function in Alzheimer’s disease

The clinical symptoms of memory loss, cognitive change and dementia that characterise Alzheimer’s disease are mirrored by a build-up of abnormal protein deposits in the brain. These include neurofibrillary tangles and amyloid plaques, defining neuropathological hallmarks of Alzheimer’s disease, the presence of which likely leads to loss of synapses and degeneration of nerve cells. Our aim is to understand the molecular mechanisms responsible for the formation of these brain inclusions, together with the neuronal loss that accompanies the clinical changes in Alzheimer’s disease.

Tau is a major component of neurofibrillary tangles and we are interested in determining how changes that occur in Alzheimer’s disease adversely influence the normal role of tau in neurons. Tau undergoes a number of post-translational modifications that impact on its function, and its interactions with other proteins, including those implicated in disease. Our recent data suggest new roles for tau that may be related to changes in neuronal activity. In this project, we will build on this work to investigate the biochemical and functional consequences of associations between protein kinases, amyloid and tau in models of Alzheimer’s disease.

Laboratory skills training includes tissue culture of primary neurons and cell lines, cell transfection, live-imaging microscopy, immunocytochemistry, gel electrophoresis, western blotting, ELISA and molecular biology methods, including DNA manipulation, PCR and cloning.

The results of this project will improve our understanding of interactions between tau and amyloid and the molecular mechanisms underlying the development of pathology in Alzheimer’s disease, and could lead to the identification of new targets for drug screening and therapy.

Applications are invited from recent graduates or final year undergraduates. Applicants should hold or expect to gain a first or upper second class honours degree (UK applicants) or equivalent. Graduates with a lower second class degree may be considered if they also hold a relevant Masters degree (Merit or Distinction).