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The role of matrix interactions in regulating the SPARC family of matricellular proteins.


Faculty of Science, Engineering and Computing

About the Project

The SPARC family of matricellular proteins determine the way in which cells respond to their extracellular environment. SPARC family proteins interact with a range of binding partners, including matrix proteins (1). They have been implicated in a range of cancers and also, in the case of SPARC, in diabetes (1-3). We have further shown that multiple alternative splice variants may also be expressed (4).

The goal of this project is to investigate the effect of specific matrix interactions in controlling the function of SPARC family proteins, and to examine how alternative splicing affects the ability of these proteins to bind matrix components. Understanding the nature and consequences of these interactions may allow us to harness the power of matricellular proteins for therapeutic use, for example to inhibit cancer progression or to support the survival/function of insulin producing beta cells, with relevance to diabetes.

The project will involve biochemical analysis of matrix binding properties of SPARC family proteins, and use molecular biology techniques to overexpress specific splice variants. The effect of matrix interactions on the functionality of SPARC family proteins will also be examined, in terms of pancreatic cancer cell proliferation, adhesion and invasion, and on the function and survival of insulin-producing beta cells.

The successful candidate will gain experience in a wide range of cell and molecular biology techniques. Full training will be provided, in addition to training in key research and transferable skills including experiment planning and design, data analysis, presentation and communication. Dr Hill recently received the 2018 Kingston University award for best project/dissertation supervisor.


Funding Notes

There is no funding for this project: applications can only be accepted from self-funded candidates

References

1). Murphy-Ullrich JE, Sage EH. Revisiting the matricellular concept. Matrix Biol. 2014 Jul; 37: 1–14.

2). Viloria K, Munasinghe A, Asher S, Bogyere R, Jones L, Hill NJ. A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1 as an inhibitor of pancreatic cancer cell growth. Sci Rep. 2016 Nov 25;6:37839.

3). Ryall CL, Viloria K, Lhaf F, Walker AJ, King AJ, Jones PM, Mackintosh D, McNeice R, Kocher HM, Flodstrom-Tullberg M, Edling EC, Hill NJ. Novel role for matricellular proteins in the regulation of islet beta cell survival: the effect of SPARC on survival, proliferation and signalling. J Biol Chem. 2014 Oct 31;289(44):30614-24.

4). Viloria K and Hill NJ. Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation. Biomol Concepts. 2016 May 1;7(2):117-132.


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