5th EuropEan MolEcular IMagIng MEEtIng - ESMI

5th EuropEan MolEcular IMagIng MEEtIng – EMIM2010
Transcription factors dynamics: from discrete pulses to oscillatory pattern to control gene
expression
Sée V.
Centre for Cell Imaging, University of Liverpool
violaine@liverpool.ac.uk
At a given time-point, cells in a population are
heterogeneous in their functions and fate and it is
therefore vital to develop and apply methods that
allow the measurement of dynamic molecular processes
in single cells. We have shown, using single
cell imaging, the critical role of nucleo-cytoplasmic
localisation oscillations of the NF-κB transcription
factor to control downstream pattern of gene transcription
(Nelson et al, Science 2004; Ashall et al,
Science 2009). NF-κB regulates cellular stress and
immune responses to infection. In most cases, oscillations
had previously been masked in population
level studies by cellular heterogeneity. We developed
a protocol based on cell treatment by repeated short
pulses of TNFα at various intervals to mimic pulsatile
inflammatory signals. This allowed obtaining
synchronous cycles of NF-κB nuclear translocation.
We have also observed cell to cell heterogeneity in
other signalling systems such as in cellular response
to low oxygen environment (hypoxia). In both inflammatory
and hypoxic signalling systems one
source of heterogeneity is due to the presence of extrinsic
dynamic processes that are functionally coupled
and that are occurring over different time scales.
We identified the cell cycle as one source of variability
as cells must coordinate and prioritise their
response to the environment depending on their
cell cycle status. We apply mathematical modelling
using the quantitative data generated by imaging
experiments to predict the role of the negative feedback,
to unravel new network motifs and to characterise
the cross-talk between the signalling systems.
EuropEan SocIEty for MolEcular IMagIng – ESMI
day1
ESMI Plenary Lecture 1 by Violaine Sée