A viral translating ribosome affinity purification (vir-TRAP) study of changesin gene expression in the hippocampal-prefrontal pathway during memory formation. (360G-Wellcome-102377_Z_13_A)

Acute pancreatitis (AP) is a potentially lethal inflammatory disease which affects approximately 50 per 100,000 individuals, costing the UK ~£1 billion per annum in patient care. Those with severe AP are more likely to develop complications and have a much higher death rate. However, existing biomarkers of AP are mostly nonspecific and unreliable, and novel approaches necessary. Mitochondrial dysfunction is a core feature of AP. Major triggers of AP, such as bile acids and alcohol metabolites, induce sustained Ca2+ levels in pancreatic acinar cells, leading to mitochondrial depolarisation, ATP depletion and necrosis. Systemic inflammation ensues and feeds back to the pancreas in a vicious cycle. Recently it has been shown that blood cell bioenergetics are altered in several diseases, assessed using the BioenergeticHealth Index (BHI), derived from mitochondrial respiratory functional analysis. Such evidence has indicated that blood cells may serve as early biomarkers of severity in inflammatory diseases. Therefore the aim of this project is to assess bioenergetic profiles of leucocytes and platelets, using a Seahorse XF24 flux analyser, from AP patients (mild/moderate/severe/critical) and normal individuals, and from murine experimental AP models (caerulein, bile acid and alcohol) with a view to possible discovery of novel biomarkers to predict severity.