Exploring the mechanism of the key signalling node, SHP2
The Babraham Institute is a world-leader in fundamental biological research investigating the systems that underpin development and healthy ageing. It is a recognised postgraduate University Partner Institute of the University of Cambridge. Starting October 2019 a number of Studentships will be available leading to a University of Cambridge PhD degree. These studentships can be awarded for up to 3.5 or 4 years. In addition, studentships funded by a range of University of Cambridge funding schemes can be held at the Babraham Institute (see the student pages of our website www.babraham.ac.uk/our-research/students/ and see:
http://www.admin.cam.ac.uk/students/studentregistry/fees/funding/index.html for specific funding sources for EU and overseas graduate students at Cambridge).
Please see our website (www.babraham.ac.uk) and the BBSRC website (http://www.bbsrc.ac.uk/funding/studentships/studentships-index.aspx) for details of eligibility and funding. Non-EU nationals must find funding for academic fees and personal support. In cases where applicants must find their own funding, we will require evidence that the level of funding is at least equal to the standard BBSRC/MRC PhD funding package. Students will join a thriving scientific community situated on an attractive parkland campus near Cambridge. Our 60 students are all members of Cambridge Colleges and participate fully in University social and academic life (www.biomed.cam.ac.uk/gradschool/).
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Full details of the project with Dr Hayley Sharpe is given below. Informal enquiries should be sent to Dr Hayley Sharpe ([Email Address Removed])
Exploring the mechanism of the key signalling node, SHP2 Cells sense their surroundings through cell surface receptors such as the Receptor Tyrosine Kinases (RTKs) which enable changes in cell behaviour (e.g. proliferation, migration) in response to various extracellular cues. Once activated, specific phosphotyrosine residues on RTKs function as docking sites to assemble a signaling complex. How the core signaling cascades are orchestrated by different RTKs to elicit distinct and specific cellular behaviours is still an open question. SHP2 (PTPN11) is a non-receptor protein tyrosine phosphatase (PTP) that functions as a key node in RTK-mediated signal transduction, acting downstream of receptors and upstream of the Ras GTPase and mitogen activated protein kinases. Furthermore, it is a clinical target in RTK-driven cancers. Despites its critical importance in determining cell signaling outcomes, its mechanism of action remains elusive.
SHP2 possesses two N terminal SH2 domains that autoinhibit its classical PTP domain. Activating SHP2 mutations that relieve this autoinhibition are associated with developmental pathologies such as Noonan syndrome and are found in several different cancers. Although there is strong evidence that its PTP domain is critical for signal propagation, its precise function remains elusive. Our lab has experience with the identification of PTP substrates using unbiased approaches (1). This project will implement biochemical analysis, cell signalling assays and quantitative proteomics, with the overall aim of elucidating SHP2 signalling mechanisms downstream of various RTKs.
This project is a collaboration between the Babraham Institute and Astra Zeneca, both located in Cambridge, therefore the student will spend a significant period of time based with the company. Candidates should have a strong academic degree in biological sciences. The successful candidate will be highly motivated, work effectively in a team setting and be interested in biochemistry, signalling and proteomics.
This studentship is available starting October 2020 and is a 4 year BBSRC-funded Industrial CASE PhD studentship. Applicant eligibility criteria for the studentship can be found here: https://www.graduate.study.cam.ac.uk/application-process/entry-requirements
Cell biology, Tyrosine phosphatases, Receptor signal transduction, Mitogen activated kinase signalling, Proteomics
Students will not be able to take up an award unless they meet all University eligibility criteria and are successful in securing admission to the University. In addition, they will not be able to apply for a visa (if needed) until they hold an unconditional offer from the University.
The closing date for the application is Tuesday, 31st March 2020. Incomplete applications will not be considered.
Please send your applications to [Email Address Removed].
Applicants should submit the following documents;
• Curriculum Vitae – including nationality and residency information, qualifications, degree result (if applicable), details of any lab based project or laboratory placements
• Covering letter
• 2 references
If you require further information about the application, please contact the Graduate Studies Assistant ([Email Address Removed]).
An Equal opportunities employer. An Institute supported by the Biotechnology and Biological Sciences Research Council
1. Fearnley GW et al. (2019) The homophilic receptor PTPRK selectively dephosphorylates multiple junctional regulators to promote cell-cell adhesion. eLife pii: e44597