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An investigation into the role of ATPase Inhibitory Factor 1 in pancreatic cancer

Helen Tanton

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This is a basic research project investigating the role of IF1 (ATP synthase inhibitory factor 1) in bioenergetics and adaptability of pancreatic cancer cells. In hypoxic or anoxic conditions, when the respiratory electron chain cannot work effectively, mitochondrial ATP synthase can switch from an ATP producer to an ATP consumer. The reverse action of ATP synthase is unfavourable for cell types that need to survive in hypoxic conditions. Among those cell types are pancreatic ductal adenocarcinoma (PDAC) cells. IF1 is a small naturally-occurring protein that inhibits the reverse (ATP-consuming) activity of ATP synthase. High expression levels of IF1 are expected to increase cell survival in hypoxic conditions. IF1 expression and its effects on cellular bioenergetics have not been characterised in PDAC. In addition to its primary function in adjusting cellular bioenergetics IF1 has been shown toregulate apoptosis. PDAC is a poorly vascularized cancer and it is therefore reasonable to hypothesise that IF1 should be abundantly expressed in PDAC cells and play a prominent role in their bioenergetics. Furthermore, highly expressed IF1 couldplay an important role in metabolic adaptation and resistance to apoptosis of PDAC cells. The key goals of the project are to test these hypotheses.

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