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SUMMARY:Evidence that sub-cellular oscillators may time and execute organe
 lle biogenesis - Jordan Raff
DTSTART:20180920T150000Z
DTEND:20180920T160000Z
UID:TALK104347@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:The accurate timing and execution of organelle biogenesis is c
 rucial for cell physiology\, yet we have little idea about how these proce
 sses are regulated. In order to study this question\, we recently establis
 hed the Drosophila centriole as a model\, as its linear structure makes it
 s biogenesis easy to define and measure. Centriole biogenesis occurs only 
 in S-phase and it is strictly regulated by Polo-like kinase 4 (Plk4). Unex
 pectedly\, we find that centriole growth in early Drosophila embryos is ho
 meostatic: When centrioles grow slowly\, they grow for a longer period\; w
 hen centrioles grow quickly\, they grow for a shorter period. This ensures
  that centrioles grow to a consistent size. Plk4 is localized at the base 
 of the growing daughter centriole and it sets both the rate and period of 
 daughter centriole growth. The activity of Plk4 kinase controls the growth
  rate\, but how Plk4 determines the growth period is unclear. I will discu
 ss our recent data that suggests that Plk4 forms an adaptive oscillator at
  the base of the growing centriole\, whose propagation times and sets the 
 duration of centriole biogenesis in Drosophila embryos. The Plk4 oscillato
 r appears to be free-running of\, but entrained and calibrated by\, the co
 re Cdk/Cyclin cell-cycle oscillator. Mathematical modelling and experiment
 al evidence indicate that Plk4 oscillations are generated by a time-delaye
 d negative-feedback loop. We speculate that such free-running oscillators 
 could regulate the timing and execution of organelle biogenesis more gener
 ally. 
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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