About the Project
Our laboratory has made significant advances in describing the molecular machinery responsible for endocytosis and recycling of integrins, and we have discovered mechanisms through which these processes drive invasion and metastasis in cancer1-4. In particular we have identified a protein which controls integrin recycling, called Rab-coupling protein (RCP), which is key to invasion and metastasis5. As well as controlling integrin recycling, we have recently found that RCP promotes trafficking of receptors of the Eph family (such as EphA2). Eph receptors are known to promote cell:cell repulsion events that cause cells to migrate away from one another, and we have new evidence that RCP is required for cell:cell repulsion in cancer. This project will be to investigate the way in which endocytosis and recycling of the EphA2 receptor is controlled by RCP, and to determine how EphA2 trafficking enables the receptor to mediate cell:cell repulsion. The project will involve live cell imaging to visualise receptor trafficking, and the use of FRET probes to look at Rho GTPase signalling as cells undergo cell:cell repulsion events. These experiments will be conducted both in vitro and in an in vivo context using genetically engineered models of cancer. This project will suite an enthusiastic young scientist who has a particular interest in receptor trafficking and cell imaging approaches.
Funding Notes
You will need at least an Upper Second Class (2.1) Honours Degree or equivalent in Life Sciences.
If you are offered a place and your native language is not English and your first or subsequent degrees were not taught in English, you will need an English Language qualification to register with the University of Glasgow.
To apply, students MUST complete the application form available on our website http://www.beatson.gla.ac.uk/education/studentships/. We do NOT accept paper applications, CVs, university transcripts or letters of reference.
References
1. Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, van den Berghe PV, von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, McKay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT, Norman JC. Rab25 and CLIC3 Collaborate to Promote Integrin Recycling from Late Endosomes/Lysosomes and Drive Cancer Progression. Dev Cell. 2012 17: 131-45.
2. Rainero E, Howe JD, Caswell PT, Jamieson NB, Anderson K, Critchley DR, Machesky L and Norman JC. Ligand-occupied integrin internalization links nutrient signaling to invasive migration. 2015. Cell Reports 10:1-16
3. Rainero E, Caswell PT, Muller PA, Grindlay J, McCaffrey MW, Zhang Q, Wakelam MJ, Vousden KH, Graziani A, Norman JC. Diacylglycerol kinase α controls RCP-dependent integrin trafficking to promote invasive migration. 2012. J. Cell Biology. 196: 277
4. Caswell, PT., Vadrevu, S. and JC. Norman. (2009). Integrins: masters and slaves of endocytic transport Nat. Rev. Mol. Cell Biol. 10(12):843-53
Bridgewater R., Norman JC, Caswell PT. (2012) Integrin trafficking at a glance. J. Cell Science 125:3695
5. Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, Cromer A, Brugge JS, Sansom OJ, Norman JC, Vousden KH (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139(7):1327-41
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