Stochasticity in Biochemical Reaction Networks (07w2139)

Arriving in Banff, Alberta Friday, June 15 and departing Sunday June 17, 2007


(University of Washington)

(California Institute of Technology)


Timeliness, relevance and importance: Understanding the dynamics biochemical reaction networks is crucial for elucidating the mechanisms involved in organism development, cancer, disease and drug discovery. Recent advances in flow cytometry, fluorescence microscopy, and other single cell measurement techniques have emphasized that these dynamics are intrinsically stochastic and that this
stochasticity may be both regulated and exploited. Furthermore, explaining data from single-cell experiments requires new mathematical models and techniques. An increased understanding of these systems will help explain newly observed phenomena and may suggest methods by which new behaviors can be engineered.

Objectives: The main goal of the workshop is to suggest new research directions and new synergies between researchers in complementary fields. To this end, the workshop will be organized around the
following questions, in approximately the order given below. The sequence of questions begins and ends with experimental evidence, in recognition of the main application of theory.

What are physical experiments and what are they telling us?

Approximately one third of the participants have performed experiments quantifying the effects of intrinsic noise on small-volume biochemical reaction networks. Their insight into the experimental results is the starting point of the workshop. The experimentalists represented here are unique in their ability to use quantitative methods and to speak the languages of mathematics, computation and control.

What are the models?

Modeling systems with enormous numbers of components in a tractable manner is by no means understood. Several of the workshop participants are pioneers in the use of stochastic processes, dynamical systems and multi-scale methods to model biochemical reaction networks.

How do we reason about them?

The inconvenient number of molecules in the cell (not a continuum and not a very small number) requires new techniques for their simulation and analysis. Several participants have developed new approaches to these problems.

How do we interconnect systems to control and regulate noise?

The signaling network in the cell is vast and only approximately known. Another third of the participants represent the forefront of control systems theory as applied to such interconnected systems. They have developed new ways to address control, stability, robustness, adaptability and uncertainty in this setting.

How can biochemical networks reliably compute?

Cells have been shown to perform sophisticated information processing. However, the underlying mechanisms are poorly understood especially in the light of intrinsic noise. Several of the participants have pioneered computation using molecules and thus are singularly prepared to address this question.

What new experiments should we do?

Measurements at the single cell level are difficult, expensive and sometimes even disappointingly uninformative. We fully expect that one of the main outcomes of this workshop will be to suggest new experiments that validate new theoretical results in this area. The combination of theoretical and applied approaches represented in this workshop makes this a particularly exciting question.