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Jenny Gallop

gallop2014Jenny Gallop PhD, Wellcome Trust Career Development Fellow, Member of the Department of Biochemistry.

Gallop Group websiteEurope PMC | Pubmed

 

Prospective PhD students and postdocs are welcome to apply with a covering email and CV to Jenny Gallop.

 

Membranes, actin and morphogenesis

gallop 2013

We are interested in the molecular basis of cell shape and the changes that occur when cells move and tissues develop. Cell shape is in large part determined by the actin cytoskeleton and remodelling of the cytoskeleton underlies the cell rearrangements that occur during normal morphogenesis and also when morphogenetic programs go wrong, for example in developmental defects and during cancer metastasis. The machinery of the actin cytoskeleton is also hijacked by various pathogens to mediate infection.

Actin filaments are nucleated at cell membranes and are elongated and bundled in different ways to form distinct cytoskeletal structures. We have found that the membrane environment influences which proteins are used to make actin structures. Membranes are interesting to consider in how cells change shape because they are the interface between the outside and inside of the cell and therefore are hubs of signalling activity, as well as being the boundary of the cell that has to be moulded by links to the cytoskeleton.

We are particularly concentrating on how actin is polymerised during filopodia formation and endocytosis. We take a two-pronged approach: (1) reconstitution of actin polymerisation in vitro using artificial membranes and Xenopus egg extracts and (2) investigation of how actin regulators are used by cells in vivo in Drosophila melanogaster and during early development in Xenopus laevis. This interdisciplinary approach gives us the possibility of attaining a complete molecular understanding and also testing those models within the natural complement of physiological signals provided by the whole organism. 

 

Selected publications:

• 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 110: 7193-7198

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

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

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

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

*joint first authors

 

groupGallop2013

Plain English

During embryonic development, a single cell divides many times generating the cells that specialize and move around to arrange themselves into the final organism through a process called morphogenesis. For the cells to get to the right locations they have to sense where they are going, exert force on their surroundings and target proteins on the membrane surface to their correct destinations. The formation of polymers of a protein called actin inside cells are important for all these functions.

Actin polymerisation is closely connected with the cell membrane, which forms the interface between the inside of the cell and its environment. We are working on two uses of actin: the formation of finger-like protrusions called filopodia, that are important for sensing the environment, and in endocytosis, which cells use to take things up and control what is in their membranes. Finding out how actin polymerisation is triggered during filopodia formation and endocytosis will help our understanding of disease and suggest ways in which we might be able to intervene. Filopodia are important for learning and memory and are used by cancer cells for metastasis. The endocytic machinery can be hijacked by pathogens to gain access to cells and actin filaments are also exploited by pathogens to reach other cells and increase infection. 

To examine how actin polymerisation is controlled by cells we generate filopodial and endocytic actin structures in test tubes using artificial membranes and cell extracts to mimic the natural interface between the cell membrane and the cytoplasm. We then study the processes that we find in embryos to find how the molecular machines are employed during morphogenesis.

Co-workers

Helen Fox • Lynn Froggett • Yoshiko Inoue • Julia Mason • Guilherme Pereira Correla • Daniel Saxton • Astrid Walrant