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The functions of the Class II Pi3-kinase signals in vivo


Project Description

Phosphoinositide lipids (PIPs) play critical roles in development and the homeostasis of adult tissues and their dysfunction has been linked to major human diseases such as cancer, diabetes, myopathies and neuropathies. We are working on an enzyme called the Class II Pi3K which generates two distinct PIP species: PI3P and PI(3,4)P2. While roles for the PI3P signal have been described, cellular functions for PI(3,4)P2 have only recently begun to emerge from studies in cell lines.

This project will address the functions of PI(3,4)P2 in vivo within a whole organism the fruit fly, Drosophila. Since PIPs, the kinases that make them and the phosphatases that degrade them, are conserved between Drosophila and mammals, we can use Drosophila as a genetically tractable model system to understand the functions of PIP signals. This project will use mutants and RNAi to manipulate the levels of kinases and phosphatases to determine how the levels of PI(3,4)P2 are controlled. A range of genetic, biochemical and cell biological techniques will then be utilised including fluorescently-tagged lipid binding domains to visualise the PIP signals in vivo and understand the impact on protein trafficking of membrane proteins such as the Notch receptor.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience or an interest in Drosophila/signalling are encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor.”

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Staiano L, De Leo MG, Persico M and De Matteis MA. Mendelian disorders of PI metabolizing enzymes. Biochim Biophys Acta 2015; 1851:867–881.

Powis KV and MacDougall LK The localisation of PtdIns3P in Drosophila fat responds to nutrients but not insulin: a role for Class III but not Class II phosphoinositide 3-kinases. Cell Signal. 2011; 23:1153–1161.

MacDougall LK, Gagou ME, Leevers SJ, Hafen E, Waterfield MD. Targetted expression of the class II phosphoinositide 3-kinase in Drosophila melanogaster reveals lipid kinase-dependent effects on patterning and interactions with receptor signaling pathways. Mol Cell Biol. 2004; 24:796-808.

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