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CATEGORIES:Isaac Newton Institute Seminar Series
SUMMARY:Formation and regulation of filopodia - Gallop\, J
  (University of Cambridge)
DTSTART;TZID=Europe/London:20151029T110000
DTEND;TZID=Europe/London:20151029T123000
UID:TALK62150AThttp://talks.cam.ac.uk
URL:http://talks.cam.ac.uk/talk/index/62150
DESCRIPTION:Filopodia are finger-like actin-rich protrusions f
 rom cells and their number\, length and turnover r
 ates are important for their functions. Their role
 s are as diverse as direction sensing by neuronal 
 growth cone filopodia\, targeting signaling during
  morphogenesis by cytonemes\, and detecting sound 
 through the stereocilia in the ear. We are using a
  two-pronged approach to elucidate the molecular b
 asis of filopodia formation: in vivo imaging of fi
 lopodia in developing Drosophila and a cell-free s
 ystem of filopodia-like structures. \n\nDrosophila
  embryos display similar phases of differentiation
  and movement to vertebrate muscles. In addition\,
  development is external (unlike mammals)\, live i
 n vivo imaging is experimentally tractable\, there
  is a wide molecular biology and genetic toolkit\,
  and Drosophila typically have less redundancy in 
 gene isoforms compared to vertebrates. Timelapse c
 onfocal imaging of developing muscles in Drosophil
 a shows intense filopodial activity during migrati
 on which diminishes as the muscles attaches to ten
 don cells in the epidermis. We show that integrins
  localise to these filopodia and signaling through
  integrins controls filopodia length and dynamics\
 , which\, in turn is needed for the arrest of migr
 ation when muscles reach tendon cell attachment si
 tes. \n\nThe cell-free system uses PI(4\,5)P2-cont
 aining supported lipid bilayers as a plasma membra
 ne mimic and frog egg extracts are used to mimic c
 ytosol. Adding extracts to the supported lipid bil
 ayers causes the nucleation of actin foci on the s
 urface and the growth of long actin bundles up fro
 m the surface. The cell-free system offers the abi
 lity to subtract and add back extracts\, fractions
  of extracts and purified proteins\, and is highly
  amenable to microscopy. We have found that initia
 tion\, but not elongation\, of filopodia-like stru
 ctures is driven by formation of the stable tip co
 mplex of actin regulators. Elongation is driven by
  dynamic proteins that are in exchange with the ti
 p complex. \n\nThis combination of biochemical dis
 section\, microscopy and genetics allows us to elu
 cidate how developmental programs and membrane env
 ironment control actin regulators to orchestrate c
 ell architecture and dynamics.\n
LOCATION:Seminar Room 2\, Newton Institute Gatehouse
CONTACT:
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