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Jenny Gallop

Membrane-triggered actin polymerization: molecular mechanisms and morphogenesis

We are interested in how different actin cytoskeletal structures inside cells are formed and how these contribute to embryonic development.

More specifically, we use in vitro reconstitution systems that combine artificial membranes and cell extracts to recreate cellular actin structures, and super-resolution and spinning disk confocal microscopy to obtain a biochemical and biophysical understanding of how multiprotein complexes responsible for actin remodeling are assembled on membranes and generate particular actin structures. The combination of membrane manipulation, nanometre-precision molecular localization, time resolution and accessible and versatile experimentation can only be achieved with such in vitro systems.

We are investigating filopodia formation in developing fly and frog embryos, and we will go back and forth between in vivo cell biological systems and in vitro assays to test and determine how molecular events inside cells generate large scale tissue movements. Early embryos are one of the only native systems where it is possible to achieve a cell biological understanding of tissue movements.

Questions we are asking include:

  • How do filopodia form?
  • In what way is the molecular mechanism of filopodia formation different from the formation of actin structures that have other arrangements of actin filaments?
  • What triggers actin polymerisation during endocytosis?
  • How will we be able to target specific actin structures in cells to find out what they contribute to cell and tissue morphogenesis?

 

Lab members: Astrid Walrant, Guilherme Pereira Correia, Yoshiko Inoue, Helen Fox, Daniel Saxton, Julia Mason, Lynn Froggett

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Key publications:

1. Gallop JL, Walrant A, Cantley LC, Kirschner MW. Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. PNAS 2013 110:7193-7198.

2. Lee K, Gallop JL, Rambani K, Kirschner MW. Self-assembly of filopodia-like structures on supported lipid bilayers. Science 2010 329:1341-1345.

3. Gallop JL, Jao CC, Kent HM, Butler PJ, Evans PR, Langen R, McMahon HT. Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J. 2006 25: 2898-2910.

4. Gallop JL, Butler PJ, McMahon HT. Endophilin and CtBP/BARS are not acyl transferases in endocytosis or Golgi fission. Nature 2005 438: 675-678.

5. McMahon HT, Gallop JL. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 2005 438: 590-596.