Signalling to the actin cytoskeleton.
Cells move during embryonic development and throughout the life of an organism. When they move, cells reorganise a system of filaments (the actin cytoskeleton) that gives them their shape and exerts force on the surrounding tissues. When regulation of the actin cytoskeleton is disrupted it can lead to cancer metastasis, intellectual disability, kidney dysfunction and other problems.
The Gallop Group studies how the actin cytoskeleton is assembled in different ways. The cell membrane is an important site of control of actin rearrangements because it is the boundary between the outside and inside of the cell and is responsible for initiating communication between and within cells, which is called signalling. We have developed cell-free systems using phospholipid bilayers and frog egg extracts that allow us to find out how signalling lipids in the cell membrane precisely control the molecular events of actin assembly. We combine these cell-free systems with the use of fruit flies, frog embryos and cultured human cells to test and generate hypotheses about the molecular events underlying actin regulation during development and in disease.
Research objectives
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How do filopodia form?
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What are the mechanisms of PI3K signalling to actin?
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How can we intervene in the regulation of actin therapeutically?
Key publications
Jarsch IK, Gadsby JR, Nuccitelli A, Mason J, Shimo H, Pilloux L, Marzook B, Mulvey CM, Dobramysl U, Bradshaw CR, Lilley KS, Hayward RD, Vaughan TJ, Dobson CL, Gallop JL (2020). A direct role for SNX9 in the biogenesis of filopodia. J. Cell Biol., 219(4):e201909178. doi: 10.1083/jcb.201909178
Richier B, Inoue Y, Dobramysl U, Friedlander J, Brown NH, Gallop JL (2018). Integrin signaling downregulates filopodia during muscle-tendon attachment. J. Cell Sci., 131(16):jcs217133. doi: 10.1242/jcs.217133
Daste F, Walrant A, Holst MR, Gadsby JR, Mason J, Lee JE, Brook D, Mettlen M, Larsson E, Lee SF, Lundmark R, Gallop JL (2017). Control of actin polymerization via the coincidence of phosphoinositides and high membrane curvature. J. Cell Biol., 216(11):3745-3765. doi: 10.1083/jcb.201704061
Urbančič V, Butler R, Richier B, Peter M, Mason J, Livesey FJ, Holt CE, Gallop JL (2017). Filopodyan: An open-source pipeline for the analysis of filopodia. J. Cell Biol., 216(10):3405-3422. doi: 10.1083/jcb.201705113
Gallop JL, Walrant A, Cantley LC, Kirschner MW (2013). Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. Proc. Natl. Acad. Sci. U.S.A., 110(18):7193-7198. doi: 10.1073/pnas.1305286110
Jenny Gallop
