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This is a fully-funded Industrial CASE PhD studentship, co-funded by BBSRC and Lilly UK, based in the Department of Neuroscience at the IoP, King’s College London (http://www.kcl.ac.uk/iop/depts/neuroscience/index.aspx). At least 6 months will be spent at Lilly UK in Erls Wood, Surrey.
Project: The microtubule-associated protein tau plays a key role in the development of Alzheimer’s disease and several related neurodegenerative diseases known as tauopathies. Tau proteins are modified in disease, becoming hyperphosphorylated and truncated, and exhibiting altered folding, aggregation and fibril formation. Tau fibrils accumulate in neurofibrillary tangles, which spread across neuroanatomically connected brain regions in well defined pathways. The presence of tangles is closely related to progressive neuronal loss and cognitive decline.
Neuroinflammation is also a prominent feature of tauopathy brain; diseased brain regions showing substantial reactive gliosis, accumulation of activated astrocytes and increased pro-inflammatory cytokine and chemokine release. In transgenic mouse models of disease, the local inflammatory environment directly influences the rate of disease progression and the extent of neurodegeneration. We have recently found that astrocyte inflammatory responses play a significant role in mediating tau phosphorylation and cleavage and the associated neuronal loss. Taken together, these findings suggest that disrupting inflammatory signalling may provide neuroprotection in AD and related tauopathies.
In this project, we will build on this work to further investigate the mechanisms by which inflammatory signalling modifies tau function and tau-associated neurodegeneration. In addition, genetic and pharmacological approaches will be used to determine the potential therapeutic benefit of modifying these pathways.
Funding Notes:
Depending on eligibility, you may be entitled to a full or partial award. A full award covers tuition fees at UK/EU rate plus a stipend of £19,000 (including supplement of £3,500 from Lilly UK). A partial award covers fees at the UK/EU rate only.
Applicants should have (or expect) a 2:1 or first class honours degree in a subject relevant to the project. If applicants already possess (or expect) a research-based MSc degree, a merit/distinction level is required. Additionally, candidates should possess an adequate level of English competence.
To apply see: http://www.kcl.ac.uk/iop/depts/neuroscience/study/pgresearch/currentopps.aspx
Interviews: Anticipated mid-September 2012.
Start date: January 2013.
References:
Garwood CJ, Atherton J, Pooler AM, Hanger DP, Noble W (2011). Astrocytes play a key role in Aβ-induced neurotoxicity and tau phosphorylation in primary culture. Cell Death and Disease. 2, e167.
Noble W, Garwood CJ, Stephenson J, Kinsey AM, Hanger DP and Anderton BH (2009). Minocycline reduces the development of abnormal tau species in models of Alzheimer’s disease. FASEB J. 23, 739-750.
Hanger DP, Anderton BH and Noble W (2009). Tau phosphorylation: The therapeutic challenge for neurodegenerative diseases. Trends Mol Medicine. 15(3), 112-119.