Discovering zinc signalling mechanisms to prevent breast cancer progression
Project aims Zinc is essential for all living cells, yet the true extent of its role is only now emerging and is fully suggestive of a complexity and importance of that attributed to calcium.
This project aims to substantiate a model for integrated zinc signalling in cells, confirming the exact role of different zinc transporters and relating the findings to the fundamental biological effects of cellular zinc. Our recent novel finding that the zinc transport ability of zinc transporters can be controlled by phosphorylation, a mechanism previously unprecedented for zinc transporters, will be examined for a direct structural and/or functional relationship with numerous cellular signalling pathways. These pathways lead to diverse cellular effects on normal processes such as growth, development and migration or, when aberrantly regulated, diseases such as cancer, diabetes and neurodegeneration ensuring the widespread application of this project.
Methods The student will use both molecular biological and cell biological techniques, already working within the group, that complement the functional investigation of the group into the workings of the ZIP family of zinc transporters. This could involve engineering mutations that allow investigation into novel activation sites within these molecules. Furthermore, there is an opportunity to investigate zinc transporter expression by immunohistochemistry in a wide range of clinical material. Additionally, there will be use of fluorescent microscopy to image zinc and monitor changes in cellular location and cell migration in relation to resistance to anti-hormones. The successful progression of the project should allow opportunities to progress findings towards clinical trial development.
Environment Dr. Kathryn Taylor, currently supported by the Wellcome Trust, is leading the field in discovering the role of ZIP family transporters in intracellular zinc signalling (3) and cancer (1, 2). The department has a large number of PhD students which ensures a lively PhD student community and also runs a fully comprehensive training programme.
This opportunity is only available to students with a scholarship to cover their funding. For further information please contact [email protected] .
1. Hogstrand C, Kille P, Nicholson RI, Taylor KM, (2009) Zinc transporters and Cancer: A potential role for ZIP7 as a hub for tyrosine kinase activation, Trends Mol Med, 15, 101-11.
2. Taylor, K.M, et al. (2008) ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in anti-hormone resistant breast cancer cells. Endocrinology. 149,4912-20.
3. Taylor, K.M. et al (2012) Protein Kinase CK2 triggers cytosolic zinc signalling pathways by phosphorylation of zinc channel ZIP7, Sci Signal. 5(710) :ra11