BBSRC Industrial CASE Studentship: The role of phosphatidylinositol 3-phosphate (PIP3) in the induction of autophagy

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Autophagy, a degradative pathway that allows the breakdown of proteins inside the cell into amino acids, is an important cellular response to nutrient limitation. Work from many groups has indicated that a small lipid molecule called phosphatidylinositol 3 phosphate (PI3P) is an important signal for nutrient sensing. By following the dynamics of several PI3P-binding proteins during amino acid (AA) starvation in live cells we have provided some clues as to the function of PI3P in autophagy induction (Axe et al, J Cell Biol 182: 685-701, 2008; Walker et al, Autophagy 16: 1093-6, 2008). We found that PI3P starts to accumulate soon after AA starvation in novel membrane compartments that we termed omegasomes. These omegasomes are in dynamic equilibrium with the endoplasmic reticulum, and they constitute sites of autophagosome production. Therefore, our recent data provide an explanation for the role of PI3P in early autophagy. The aims of this studentship will be to further explore the role of PI3P in autophagy induction. The majority of the work will involve methods for the visualization of PI3P in omegasomes, during the earliest stages of the starvation response. A second aim will be the identification of the 3-phosphatase that terminates the PI3P signal.

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