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A Targeted Brain Proteomic Study Linking Diet, Ageing and Cognition

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  • Full or part time
    Dr L Williams
    Dr R Langston
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Supervisors: Dr Lynda Williams, Dr Rosamund Langston (University of Dundee) & Dr Fiona Campbell

We have recently identified that the gene serpinA3n encoding the acute phase protein alpha-1 antichymotrypsin (aACT) is up-regulated by a diet high in saturated fat and sugar in the hypothalamus and hippocampus of the brain in a widely used mouse model of diet induced obesity and insulin insensitivity (1). Insulin insensitivity and neuronal inflammation are related to cognitive decline. SerpinA3n gene expression also increases with age in mice (Williams et al unpublished results). The function of the protein aACT in the brain has not been completely elucidated but aACT is known to form complexes with apolipoprotein E (ApoE) and protein amyloid β and is an integral component of the plaques found in Alzheimer's disease (2).

The present project seeks to investigate the role of aACT in the rodent brain. The fate and function of aACT in the brain will be identified using a targeted proteomic approach including co-immunoprecipitation and mass spectroscopy. Hippocampus-dependent memory function will be correlated with brain inflammation and aACT levels using behavioural measures of episodic memory in rodents to investigate the relationship between age, diet, inflammation and cognition.

Funding Notes

Applicants for a studentship must have obtained, or be about to obtain, an upper second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology.

These studentships are available to UK and other EU nationals (due to funding criteria, EU nationals MUST have resided in the UK for three years prior to commencing the studentship) and provides funding for tuition fees and stipend, subject to eligibility.

References

1. Winzell, MS, Ahren, B: The High-Fat Diet-Fed Mouse: a Model of Studying Mechanisms and Treatment of Impaired Glucose Tolerance and Type 2 Diabetes. Diabetes 53 Suppl 3: 5215-5219, 2004.

2. Potter, H, Wefes, IM, Nilsson, LN: The Inflammation-Induced Pathological Chaperones ACT and apo-E are Necessary Catalysts of Alzheimer Amyloid Formation. Neurobiol Aging 22: 923-930, 2001.

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