Revealing how extracellular matrix glycans define chemokine gradients (360G-Wellcome-211912_Z_18_Z)
The diffusion of chemokines in the extracellular matrix is a requirement for the formation of chemokine gradients that guide immune cell migration to sites of inflammation, and controlled by matrix glycans of the glycosaminoglycan family. The focus of this research is to use well-defined models of the extracellular matrix to probe the interaction between the chemokine CXCL12 and the glycosaminoglycan heparan sulphate, and how this defines the mobility of CXCL12. The first key goal of the project is to design and produce a fluorescently-tagged CXCL12 mutant with modulated glycosaminoglycan binding which can be compared against the wild-type chemokine and other mutants already available. The second key goal is to use the biophysical method of fluorescence recovery after photobleaching to characterise the differential diffusion of mutant and wild-type CXCL12 in glycosaminoglycan-rich matrices. This project thus combines biochemistry and biophysics to gain a better understanding of the molecular mechanisms underpinning the formation of chemokine gradients in extracellular matrix.
£0 31 May 2018