Speaker: Ping Ao, Dept of Mech Eng & Physics, U Washington

Title: Modeling the Stability and Robustness of Phage Lambda Genetic Switch

Abstract:
Recently there are tremendous activities on the study of bio-switch, ranging
from both living organisms to synthetic ones, from mathematical explorations
of the structure to detailed numerical calculations of specific ones. One of
the outstanding problems was the stability of lambda switch, arguably the
simplest living genetic switch and the origin of molecular biology. Despite
more than 40 years detailed experimental and theoretical study, it was found
that theoretically or mathematically we could not model the robustness
displayed by biological experiments on lambda switch with all the necessary
constraints from physics and chemistry. This poses a serious challenge for
computational/theoretical biologists in the era of systems biology:	
How could theorists provide an insightful understanding to real biological
systems if they could not even understand the simplest organism?

In my talk, I will discuss a successful systems biology approach to this
outstanding problem, by integrating relevant information at all levels:
physics, chemistry, DNA, protein, function. It allows us a parameter-free
modeling: in making predictions, all our parameters are fixed by other
experimental measurements. In additional to obtaining a quantitative
agreement between known experimental data, one of our predictions was
recently confirmed by an independent experiment. We believe that we have
finally understood the stability puzzle mathematically.

I will also discuss a new mathematical modeling method growing out of our
lambda study. This method appears particularly suitable to discuss
robustness problem and have a deep connection to the core of theoretical
physics.


On literature relevant to my talk:

   There are too many good articles on robustness and bio-switch. Here I
mention two reviewing current interesting questions:
1)   Kitano H 
      Biological robustness 
      NATURE REVIEWS GENETICS 5 (11): 826-837 NOV 2004

    The best place to get the biological background on genetic switch is the
book: 
2) Pashne M,  A Genetic Switch, either 2nd edition (1992) or 3rd edition
(2004). 

    Our papers on modeling lambda switch can be found in
3) Zhu, Yin,  Hood, Ao,
    Functional and Integrative Genomics 4 (2004) 188-195.
4) Zhu, Yin, Hood, Ao,
     Journal of Bioinformatics and Computational Biology 2 (2004) 785-817. 

    For a discussion of our new mathematical method, see 
5)  C. Kwon, P. Ao, D.J. Thouless, 
       Proc. Natl. Acad. Sci. (USA) 102 (2006) 130029-13034. 
6)  P Ao
       Journal of Physics A37 (2004) L25-L30.
	
7) Organisms employ both positive and negative feedbacks in their control.	
     A discussion of control theory from the physicists point of view can
be found in
       J. Bechhoefer,  Rev. Mod. Phys. 77 (2005) 783-1080.