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Dr K Taylor
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
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 molecular biological techniques to generate their own unique zinc transporter mutations by site-directed mutagenesis, transfect them into mammalian cells (3, 7, 8) and investigate any alteration in protein function and zinc transport using a range of cell biological techniques (3), most of which are currently in use within the group, to examine signalling activation, molecular dimerisation and cellular end points such as growth, proliferation and migration. Additionally, there will be use of fluorescent microscopy to image changes in zinc fluorescent dyes in response to intracellular zinc (3) and monitor changes in cellular location and cell migration. The successful progression of the project should also allow opportunities to investigate findings in relation to breast cancer development.
Environment
Dr. Kathryn Taylor, currently supported by the Wellcome Trust, is leading the field in discovering the role of ZIP family transporters (7, 8, 9) in intracellular zinc signalling (1) and cancer (1, 3, 4). The department has a large number of PhD students which ensures a lively PhD student community and also runs a fully comprehensive training programme.
For further information please contact [Email Address Removed] stating the project title that you are interested in.
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 molecular biological techniques to generate their own unique zinc transporter mutations by site-directed mutagenesis, transfect them into mammalian cells (3, 7, 8) and investigate any alteration in protein function and zinc transport using a range of cell biological techniques (3), most of which are currently in use within the group, to examine signalling activation, molecular dimerisation and cellular end points such as growth, proliferation and migration. Additionally, there will be use of fluorescent microscopy to image changes in zinc fluorescent dyes in response to intracellular zinc (3) and monitor changes in cellular location and cell migration. The successful progression of the project should also allow opportunities to investigate findings in relation to breast cancer development.
Environment
Dr. Kathryn Taylor, currently supported by the Wellcome Trust, is leading the field in discovering the role of ZIP family transporters (7, 8, 9) in intracellular zinc signalling (1) and cancer (1, 3, 4). The department has a large number of PhD students which ensures a lively PhD student community and also runs a fully comprehensive training programme.
For further information please contact [Email Address Removed] stating the project title that you are interested in.
Funding Notes
Self funded students only
References
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 KM, (2008) A distinct role in breast cancer for two LIV-1 family zinc transporters, Biochem Soc Trans, 36, 1247-51.
3. 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.
4. Taylor, K.M., et al., (2007) The emerging role of the LIV-1subfamily of zinc transporters in breast cancer, Molecular Medicine, 13 l, 396-406.
5. Taylor, K.M., et al. (2005) Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. FEBS Letters 579, 427-32.
6. Taylor KM, Hiscox S,Nicholson RI.(2004) Zinc transporter LIV-1;A link between cellular development and cancer progression.Trends Endocrin and Metab,15, 461-463.
7. Taylor, K.M., Morgan, H.E., Johnson, A. & Nicholson, R.I., (2004) Structure-Function Analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochem J. 377, 131-139.
8. Taylor, K. M., et al., (2003) Structure-Function Analysis of LIV-1, the breast cancer associated protein that belongs to a new subfamily of zinc transporters. Biochem. J. 375, 51-59.
9. Taylor K.M. and Nicholson R.I. (2003) The LZT proteins; the new LIV-1 subfamily of zinc transporters. BBA biomembranes,1611, 16-30
2. Taylor KM, (2008) A distinct role in breast cancer for two LIV-1 family zinc transporters, Biochem Soc Trans, 36, 1247-51.
3. 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.
4. Taylor, K.M., et al., (2007) The emerging role of the LIV-1subfamily of zinc transporters in breast cancer, Molecular Medicine, 13 l, 396-406.
5. Taylor, K.M., et al. (2005) Structure-function analysis of a novel member of the LIV-1 subfamily of zinc transporters, ZIP14. FEBS Letters 579, 427-32.
6. Taylor KM, Hiscox S,Nicholson RI.(2004) Zinc transporter LIV-1;A link between cellular development and cancer progression.Trends Endocrin and Metab,15, 461-463.
7. Taylor, K.M., Morgan, H.E., Johnson, A. & Nicholson, R.I., (2004) Structure-Function Analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters. Biochem J. 377, 131-139.
8. Taylor, K. M., et al., (2003) Structure-Function Analysis of LIV-1, the breast cancer associated protein that belongs to a new subfamily of zinc transporters. Biochem. J. 375, 51-59.
9. Taylor K.M. and Nicholson R.I. (2003) The LZT proteins; the new LIV-1 subfamily of zinc transporters. BBA biomembranes,1611, 16-30
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