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SUMMARY:Formation and regulation of filopodia - Gallop\, J (University of 
 Cambridge)
DTSTART:20151029T110000Z
DTEND:20151029T123000Z
UID:TALK62150@talks.cam.ac.uk
CONTACT:42080
DESCRIPTION:Filopodia are finger-like actin-rich protrusions from cells an
 d their number\, length and turnover rates are important for their functio
 ns. Their roles are as diverse as direction sensing by neuronal growth con
 e filopodia\, targeting signaling during morphogenesis by cytonemes\, and 
 detecting sound through the stereocilia in the ear. We are using a two-pro
 nged approach to elucidate the molecular basis of filopodia formation: in 
 vivo imaging of filopodia in developing Drosophila and a cell-free system 
 of filopodia-like structures. \n\nDrosophila embryos display similar phase
 s of differentiation and movement to vertebrate muscles. In addition\, dev
 elopment is external (unlike mammals)\, live in vivo imaging is experiment
 ally tractable\, there is a wide molecular biology and genetic toolkit\, a
 nd Drosophila typically have less redundancy in gene isoforms compared to 
 vertebrates. Timelapse confocal imaging of developing muscles in Drosophil
 a shows intense filopodial activity during migration which diminishes as t
 he muscles attaches to tendon cells in the epidermis. We show that integri
 ns localise to these filopodia and signaling through integrins controls fi
 lopodia length and dynamics\, which\, in turn is needed for the arrest of 
 migration when muscles reach tendon cell attachment sites. \n\nThe cell-fr
 ee system uses PI(4\,5)P2-containing supported lipid bilayers as a plasma 
 membrane mimic and frog egg extracts are used to mimic cytosol. Adding ext
 racts to the supported lipid bilayers causes the nucleation of actin foci 
 on the surface and the growth of long actin bundles up from the surface. T
 he cell-free system offers the ability to subtract and add back extracts\,
  fractions of extracts and purified proteins\, and is highly amenable to m
 icroscopy. We have found that initiation\, but not elongation\, of filopod
 ia-like structures is driven by formation of the stable tip complex of act
 in regulators. Elongation is driven by dynamic proteins that are in exchan
 ge with the tip complex. \n\nThis combination of biochemical dissection\, 
 microscopy and genetics allows us to elucidate how developmental programs 
 and membrane environment control actin regulators to orchestrate cell arch
 itecture and dynamics.\n
LOCATION:Seminar Room 2\, Newton Institute Gatehouse
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