PhD Studentship: Targeting WW domain function to prevent tumour progression



Deadline: 20 January 2014.

Start Date: October 2014

Supervisory Team: Dr Tharin Blumenschein, Email: [email protected]

The Project:

This project will use NMR spectroscopy to study the interactions between WWP2 (an E3 ubiquitin ligase of the Nedd4 family) and peptides from its binding targets, with the goal of design peptides capable of inhibiting these interactions specifically. When overexpressed in animal models, WWP2 has been shown to increase tumour spread. Altered expression of its isoform WWP2-N was observed in prostate cancer and melanoma.

WWP2 contains a Ca2+/phospholipid binding C2 domain, four WW domains, and a HECT ligase catalytic domain. Through the WW domains, WWP2 can interact with a number of substrates, including PTEN (a tumour suppressor gene which is often lost in cancers), Smads (part of the TGF-b signalling pathway, deregulated in a number of cancers), and the stem-cell specific transcription factor Oct4 (involved in cancer cell proliferation, dedifferentiation, and chemotherapy resistance). The different binding partners of WWP2 are all involved in regulating cell proliferation and differentiation, resulting in WWP2’s involvement in different types of cancer. Peptides specific for different targets can be used both as a tool to understand the biological role of those interactions, and as a starting point for the design of future peptidomimetics anticancer therapies. Specific peptides will be designed based on the structural information. Cell-penetrating peptides will be tested for their effects on cancer cell growth and apoptosis in cell cultures.

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The student will receive training in molecular biology techniques, protein expression and purification, NMR spectroscopy, cell culture techniques, and other techniques for studying protein-protein interactions.

Entry Requirements:

First degree (2.1) in Chemistry, Physics, Biochemistry or related subjects.

Funding:

This project is funded by The Big C for three years and due to funding restrictions is open to applications from the UK/EU.

An annual stipend of £14,639 is available to the successful candidate.

Making Your Application:

Please apply via the University’s online application system, via the ‘Apply’ button below.

NB: Applications are processed as soon as they are received, so early application is encouraged.

To discuss the application process or particular projects, please contact the: Admissions Office, email: [email protected] or telephone +44 (0)1603 591709. 

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