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(BBSRC DTP) Understanding how cell growth is controlled by nutrient signalling


Project Description

The ability of organisms to modify their growth according to environmental conditions is a fundamental principle in nature, whilst uncontrolled growth is a hallmark of cancer and several other diseases. To grow, cells must expand their surface membrane and cellular contents in a co-ordinated way. All eukaryotes use a conserved environment-sensing system (termed Target of Rapamycin: TOR) to sample growing conditions and respond by producing new cell constituents (lipids and proteins). However, we know almost nothing about how environment sensing promotes the incorporation of these constituents into new cell surface membrane to drive growth. Here we will focus on surface membrane proteins, made in the endoplasmic reticulum and then transported through the secretory pathway to the cell surface. We will test whether TOR controls membrane protein transport by regulating the formation of COP-II transport vesicles at the ER, and by regulating COP-I mediated transport within the Golgi complex. As a prelude to detailed studies within a PhD programme, we will test whether TOR controls the phosphorylation of COP-I/COP-II vesicle components and how TOR signalling influences the rate of membrane protein transport along the secretory pathway.

http://www.manchester.ac.uk/research/philip.woodman/
http://www.manchester.ac.uk/research/martin.lowe/
http://www.manchester.ac.uk/research/chiara.francavilla/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP 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

[1] Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell 2017;168:960-76.
[2] Barlowe C, Helenius A. Cargo Capture and Bulk Flow in the Early Secretory Pathway. Ann. Rev. Cell Dev. Biol. 2016; 32: 197-222.
[3] Witcos M, Lowe M. Recognition and tethering of transport vesicles at the Golgi apparatus. Curr. Opin. Cell Biol. 2017; 47: 16-23.
[4] Francavilla, C. et al. Multilayered proteomics reveals molecular switches dictating ligand-dependent EGFR trafficking. Nat. Struct. Mol. Biol. 23, 608-618 (2016).

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