Project Title: The interplay of endocytosis and signalling

Project supervisor: Professor Elizabeth Smythe (BMS and CMIAD)

Application deadline: Friday 14 December 2012.

Project description:

Endocytosis allows the cellular uptake of a variety of biologically important macromolecules including nutrients and signaling molecules. An emerging paradigm is that interactions between the endocytic pathway and intracellular signaling are key to fine-tuning signalling output in developmental and organismal contexts. This may occur via the establishment of ‘signalosomes’, specialized membrane microdomains that increase signal specificity and intensity. Ongoing studies in the lab are focusing on the establishment of signalosomes in primary endothelial cells as well as using Drosophila as a model system.

Project: How does hRME-6, a rab5GEF, integrate trafficking and signaling?

We have implicated hRME-6 in the establishment of functional pools of rab5 involved in signalling and trafficking. This project will explore the dynamics of membrane microdomains using a combination of biochemistry, microscopy and cell-based assays.

Relevant references:

1. Semerdjieva S, Shortt B, Maxwell E, Singh S, Fonarev P, Hansen J, Schiavo G, Grant BD, Smythe E. (2008)
   Coordinated regulation of AP2 uncoating from clathrin-coated vesicles by rab5 and hRME-6. J
   Cell Biol. 2008 183:499-511.
2. Kholodenko BN. FEBS Lett. 2009
   Spatially distributed cell signalling. 583:4006-12.
3. Sorkin A, von Zastrow M. (2009)
   Endocytosis and signalling: intertwining molecular networks.
   Nat Rev Mol Cell Biol. 10:609-2

Contact details:

Professor Elizabeth Smythe

Email: E.Smythe@sheffield.ac.uk

Web: http://www.shef.ac.uk/bms/research/esmythe