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.

Principal eigenvalue of an elliptic operator with large advection and its applications to evolution of dispersal

Speaker: 

Associate Professor Yuan Lou

Institution: 

The Ohio State University

Time: 

Thursday, February 7, 2008 - 11:00am

Location: 

MSTB 254

We investigate the asymptotic behavior of the principal eigenvalue of an elliptic operator as the coefficient of the advection term approaches infinity. As a biological application, a Lotka-Volterra reaction-diffusion-advection model for two competing species in a heterogeneous environment is studied. The two species are assumed to be identical except their dispersal strategies: both species disperse by random movement and advection along environmental gradients, but one species has stronger biased movement than the other one. It is shown that at least two scenarios can occur: if only one species has a strong tendency to move upward the environmental gradients, the two species will coexist; if both species have such strong biased movements, the species with the stronger biased movement will go to extinct. These results provide a new mechanism for the coexistence of competing species, and they also suggest that an intermediate biased movement rate may be evolutionary stable.

Resolution of Singularities and Analysis

Speaker: 

Professor Michael Greenblatt

Institution: 

SUNY Buffalo

Time: 

Tuesday, January 15, 2008 - 2:00pm

Location: 

MSTB 254

We will describe some recent applications of resolution of singularities methods to questions of interest in analysis. In particular, we will describe a recent local resolution of singularities algorithm of the speaker for real-analytic functions. This algorithm is elementary and self-contained, and makes extensive use of Newton polyhedra and local coordinate systems. Some applications will be given. These include applications to oscillatory integrals, asymptotic expansions for sublevel set volumes, and the determination of the supremum of the positive e for which |f|^{- e} is locally integrable. Here f denotes a real-analytic function.

On the Toda and Ablowitz-Ladik equations: comparing two discrete completely integrable systems

Speaker: 

Courant Instructor Irina Nenciu

Institution: 

Courant Institute, NYU

Time: 

Monday, January 14, 2008 - 3:00pm

Location: 

MSTB 254

Completely integrable systems are remarkable evolution equations, the best known of which is probably the Korteweg-deVries equation. Their many "symmetries", or conserved quantities, often allow for a detailed and in-depth description of their solutions.

We will present a number of new results concerning the Ablowitz-Ladik equation (AL). This is a classical, completely integrable discretization of the nonlinear Schroedinger equation. We will contrast its properties with those of one of the most celebrated discrete integrable system, the Toda lattice, while also illustrating the varied nature of the tools and ideas involved in the theory of completely integrable systems: geometric, algebraic, and functional analytic, among others.

Switches, oscillations, and the dynamics of monotone dynamical systems

Speaker: 

Postdoctoral Fellow German Enciso

Institution: 

Harvard University

Time: 

Monday, January 7, 2008 - 2:00pm

Location: 

Nat Sci II 1201

Determining the long-term behavior of large biochemical models has proved to be a remarkably difficult problem. Yet these models exhibit several characteristics that might make them amenable to study under the right perspective. One possible approach (first suggested by Sontag and
Angeli) is their decomposition in terms of so-called monotone systems, which can be thought of as systems with exclusively positive feedback.

In this talk I discuss some general properties of monotone dynamical systems, including recent results regarding their generic convergence
towards an equilibrium. Then I will discuss the use of monotone systems to model biochemical behaviors such as switches and oscillations under
time delays.

Rational curves on algebraic varieties

Speaker: 

Profesor Stefan Kebekus

Institution: 

University of Cologne, Germany

Time: 

Friday, December 7, 2007 - 4:00pm

Location: 

MSTB 254

One approach to investigate the structure of an algebraic variety X is to study the geometry of curves, especially the rational curves, that X contains. This approach relies on classical geometric ideas and strives to understand the intrinsic geometry of varieties. It is nowadays understood that if X contains many rational curves, then their geometry determines X to a large degree.

After Shigefumi Mori showed in his landmark works that many interesting varieties contain rational curves, their systematic study became a standard tool in algebraic geometry. The spectrum of application is diverse and covers long-standing problems such as deformation rigidity, stability of the tangent bundle, classification problems, and generalizations of the Shafarevich hyperbolicity conjecture.

The talk concentrates on examples and basic properties of minimal degree rational curves on projective varieties. Some of the more advanced applications will be discussed.

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