Michael R.H. White talks with
ScienceWatch.com and answers a few questions about
this month's Emerging Research Front Paper in the field of
Biology & Biochemistry.
Article: Oscillations in NF-kappa B signaling control
the dynamics of gene expression
Authors: Nelson, DE, et al.
Journal: SCIENCE, 306 (5696): 704-708 OCT 22 2004
Addresses: Ctr Cell Imaging, Sch Biol Sci, Biosci Res
Bldg,Crown St, Liverpool L69 7ZB, Merseyside, England.
Ctr Cell Imaging, Sch Biol Sci, Liverpool L69 7ZB, Merseyside,
Univ Manchester, Inst Sci & Technol, Dept Chem, Manchester
M60 1QD, Lancs, England.
(addresses have been truncated.)
Why do you think your paper is highly
This paper was the first experimental description of NF-?B oscillations in
single cells. This represented a new way of thinking about this
well-studied pathway. We also provided direct evidence that continuation of
the oscillations also resulted in maintenance of gene expression. The paper
included the application of a mathematical model to study the system. This
has been recognized as a leading example of predictive systems biology.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
Yes, the study used state-of-the-art cell imaging to show a process that
for most people was entirely unexpected. A further key attribute was that
it was a systems biology study that involved both mathematical and
Would you summarize the significance of your paper in
"In the long term, our new understanding of this
system may allow for the development of new types
of treatments for inflammatory
It has often been assumed that signaling through NF-?B may depend simply on
the amount of NF-?B that enters the nucleus. This can be described in terms
of "amplitude" or the control can be described as being obtained through
"amplitude modulation (AM)."
We found that NF-?B, rather like calcium signaling, shows oscillatory
behavior. It has long been shown that calcium signaling can carry
information in the timing between the peaks. This can be described in terms
of "frequency" or the control can be described as being through "frequency
Our results in the Nelson et al., paper suggested that NF-?B had
the potential characteristics of a protein-based signaling system that
might use frequency modulation to carry information. Our recent paper in
Science by L. Ashall, et al., "Pulsatile stimulation
determines timing and specificity of NF-?B-dependent transcription,"
242-6, April 10, 2009, has provided direct evidence for this hypothesis.
How did you become involved in this research and were
any particular problems encountered along the way?
The research arose from an initial collaboration with AstraZeneca. The key
problems lay in establishing the long-term microscopy experiments which
became possible when we moved to temperature controlled rooms in a new
Where do you see your research leading in the
The paper has recently led on to a further paper in Science (as
noted above) where we have provided direct experimental evidence that the
frequency of oscillations does indeed control which genes are switched on.
We have also used mathematical models to predict the source and perhaps a
role for heterogeneity in the timing of the oscillations between cells.
Overall, this work is relevant for understanding the propagation and
resolution of inflammation in cells and tissues. At the same time, the
principles that lie behind the mechanism of action of this system might
also be relevant to understanding other signaling systems.
Do you foresee any social or political implications for
In the long term, our new understanding of this system may allow for the
development of new types of treatments for inflammatory disease.
Professor Michael R.H. White, Ph.D.
School of Biological Sciences
University of Liverpool
Liverpool, UK Web