Functional role of presynaptic tau during aging and Alzheimer’s disease
1 fully funded 4-year BBSRC CASE studentship with AstraZeneca.
Tau is a microtubule stabilizing protein primarily localized to the axonal region of neurons but is also found in synapses. The functional significance of tau in the synapse is not fully understood. Recent studies have shown that important synaptic functions including neurotransmission are disrupted when altered forms of tau, such as found in Alzheimer’s disease, interact with pre-synaptic vesicles. Activity-dependent tau release from synapses is also thought to be important for normal physiological functions of tau and the trans-synaptic propagation of abnormal tau in Alzheimer’s disease. However, the relationship between tau-mediated functional changes to synapse activity and tau release have not yet been thoroughly investigated.
The aim of this project is to use long-term organotypic brain slice cultures to investigate the functional significance of tau mislocalisation to the pre-synapse, including the effect of aging and disease on the interaction of tau with synaptic vesicles, the implications of these interactions for tau release and how this relates to synapse function. We intend to characterise changes in synaptic vesicle mobility and tau localisation to the pre-synapse tau during aging and disease, determine the effects on tau release and synapse function of blocking the tau-synaptogyrin-3 interaction, and to identify the residues within tau and synaptogyrin-3 that interact. This knowledge will be used to determine if interfering with the tau-synaptogyrin-3 interaction corrects tau-associated neurodegenerative pathways in aging and disease. Time-permitting, key findings will also be studied in human neurons.
The student will acquire cutting-edge cell culture, biochemical and molecular biology techniques and will use state-of-the-art microscopy equipment available to us in our Nikon Imaging Centre. The student will join leading research teams, based in the newly established Maurice Wohl Clinical Neuroscience Institute at King’s College London. The student will also benefit from the significant expertise of the Industrial supervisor, Dr Robyn McAdam, and will gain experience of working in laboratories at AstraZeneca with access to their facilities, resources and experience. This will involve the student undertaking a 3-6 month placement at AstraZeneca in Cambridge.
Applicants should have (or expect to obtain) a 2:1 or 1st class bachelor’s degree in neuroscience or related biomedical science, or the overseas equivalent. If applicants possess (or expect to obtain) a research-based MSc degree, a merit or distinction level is required.
The award covers an enhanced PhD stipend, tuition fees costs towards travel expenses and laboratory consumables.
The funding available supports Home/EU students within standard research council restrictions. Home/EU students are only eligible for a full studentship if they have lived and studied or worked within the UK for three years prior to the funding commencing.
Unfortunately, we cannot accept applications from home/EU applicants who do not fulfil these eligibility criteria or from overseas candidates.
References must be received by the deadline for the applicant to be eligible.
Only shortlisted applicants will be contacted.
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