Kolmogorov's work and similarities between chaotic and rigid dynamical systems

Speaker: 

Professor Don Ornstein

Institution: 

Stanford

Time: 

Thursday, May 29, 2008 - 4:00pm

Location: 

MSTB 254

This will be a non-technical talk. I will start by describing how Kolmogorov models dynamical systems and stationary processes so as to put them both into the same mathematical framework and some results that are made possible by this point of view.

These results lie on the chaotic side of dynamics.

On the rigid side of dynamics, I will describe the Kolmogorov-Moser twist theorem (part of KAM theory) and a generalization of that theorem.

I will discuss the very strong similarities between the stability properties of
chaotic and rigid systems.

Exploring structure, function, and dynamics of biochemical networks

Speaker: 

Ilya Nemenman

Institution: 

Los Alamos National Laboratory

Time: 

Monday, March 3, 2008 - 3:00pm

Location: 

NS1 1114

In a recent article in APS News, John Hopfield, one of the founders of what has now become quantitative and systems biology, has defined physics as "The idea ... that the world is understandable." As a physicist working on biological problems, I pursue this understanding as the ultimate goal. Unfortunately, even for the simplest cellular networks, understanding their function is often obscured behind long and incomplete part lists of interaction partners, wiring diagrams, and differential equations. In this talk, I will describe how ideas of statistical physics and information theory allow us to make small steps towards formulation of and answers to questions like: What are the signal processing capabilities of stochastic biochemical networks? Which functions can they perform? How important is stochasticity? How can we understand network dynamics without microscopic simulations? While addressing these questions, I will also show examples of cross-fertilization between physics and systems biology: on the one hand, physics will suggest tools for faster simulation and deeper understanding of the networks dynamics, and, on the other, study of a biological problem will show an unexpected and illuminating connection between seemingly unrelated areas of theoretical physics.

From Temperature to Pain: thermal responses and motor behavior of E. coli and C. elegans.

Speaker: 

Associate Research Scholar William Ryu

Institution: 

Princeton University

Time: 

Tuesday, March 11, 2008 - 10:00am

Location: 

NSII 2201

E. coli has a natural behavioral variable---the direction of rotation of its flagellar rotary motor. Monitoring this one-dimensional behavioral response in reaction to chemical perturbation has been instrumental in the understanding of how E. coli performs chemotaxis at the genetic, physiological, and computational level. We are applying this experimental strategy to the study of bacterial thermotaxis - a sensory mode that is less well understood. To investigate bacterial thermosensation we subject single cells to well defined thermal stimuli such as impulses of heat produced by an IR laser and analyze their response. Higher organisms may have more complicated behavioral responses because their motions have more degrees of freedom. Here we provide a comprehensive analysis of motor behavior of such an organism -- the nematode C. elegans. Using tracking video-microscopy we capture a worm's image and extract the skeleton of the shape as a head-to-tail ordered collection of tangent angles sampled along the curve. Applying principal components analysis we show that the space of shapes is remarkably low dimensional, with four dimensions accounting for > 95% of the shape variance. We also show that these dimensions align with behaviorally relevant states. As an application of this analysis we study the thermal response of worms stimulated by laser heating. Our quantitative description of C. elegans movement should prove useful in a wide variety of contexts, from the linking of motor output with neural circuitry to the genetic basis of adaptive behavior.

Mathematical Modeling of Synthetic Networks Reveals Noise-induced Gene Regulation Mechanisms.

Speaker: 

Research Associate Xiao Wang

Institution: 

Boston University

Time: 

Monday, March 10, 2008 - 12:00pm

Location: 

NSII 3201

Bistable systems are very common modules in natural biological systems. In this work, well-characterized biological components are used to construct a genetic toggle switch in S. cerevisiae through mutual inhibition. Mathematical modeling is combined with molecular biology to design and construct the genetic toggle switch. We show that, guided by modeling predictions, we can achieve bistability by tuning the system. I will illustrate the artificial "cell differentiation", both experimentally and mathematically, by starting the switch from a specific initial condition that expressions of both repressors are turned off.

This work demonstrates the use of synthetic gene networks to uncover general regulatory mechanisms in natural biological systems.

About the speaker: Dr. Xiao Wang is currently a Research Associate working with Dr. James Collins at Boston University's Center for BioDynamics. There he is developing mathematical models and computational algorithms to help understand and construct complex synthetic networks in eukaryotic cells from bottom up. Dr. Wang received his Ph.D. in Operations Research/ Bioinformatics & Computational Biology from The University of North Carolina at Chapel Hill in 2006. During his Ph.D., Dr. Wang also studied the yeast pheromone response pathway and used mathematical models to uncover novel regulatory roles of MAP kinase.

Modeling complex cell differentiation decisions: from competitive heterodimerization to the C. elegans germline

Speaker: 

Olivier Cinquin

Institution: 

University of Wisconsin, Madison

Time: 

Tuesday, February 26, 2008 - 11:00am

Location: 

NS2 4201

How cells determine or lose their identity is a key question in the study of development and carcinogenesis. Differentiation is regulated by a variety of factors that interact in networks. Intriguingly, some complex differentiation decisions involving many possible outcomes are not easily reduced to a defined series of binary fate decisions. I have approached the mechanism by which cells make such complex decisions in two ways.

First, in a "top-down" approach, I asked which classes of simple network designs could provide sufficiently rich behavior to account for differentiation decisions. Competitive heterodimerization networks, which are present in numerous developmental and physiological contexts, stand out as being particularly flexible. Modeling of these networks suggests unforeseen biological functions.

Second, in a "bottom-up" approach, I started to address a tractable, "real-world" experimental model of a complex differentiation decision. I chose a three-way differentiation decision made in the C. elegans germline, which provides a genetic network that has been extensively characterized. I showed experimentally that differentiation is controlled by positional and timing mechanisms. These results lay the groundwork for a systems biology analysis of differentiation in the C. elegans germline.

An important challenge for the future is to comprehensively characterize a given experimental model, by building on the understanding of simple networks that are amenable to mathematical study.

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