November 2011

Systems biology

Biochemical networks in space and time  

BY SteVen AltsChuler and Alexander Hoffmann



Meetings_systems_biologyWith DNA sequencing costs falling faster than Moore’s law, the challenge is less to discover what is in the genome but how the biological molecules interact to produce biological function. Molecular interactions are often multivalent to produce complex networks. Biochemical networks operate in time to determine cellular responses to environmental changes and in space within and across boundaries and organelles, and they are subject to the physical laws that apply to all molecules, including the fundamental stochasticity of molecular interactions and chemical reactions. Given data quantities and the potential for complexity that exceed even well-honed, intuitive reasoning, a hallmark of the systems biology approach is to combine experiment and modeling to formulate and test hypotheses. The sessions below were designed to highlight approaches that derive and reveal behaviors of complex networks on molecular, time and distance scales.

Network assembly 

The first session will address novel approaches that allow for assembly of large network models containing many components. Trey Ideker (University of California, San Diego) will describe strategies to combine high-throughput genetic and physical interaction data sets as well as recent work revealing how some aspects of networks change in response to DNA damage and how others do not.

Nevan Krogan (University of California, San Francisco) will describe approaches and insights gained from characterizing the physical interaction network within mammalian cells and how intruding pathogen proteins harness and manipulate it.

Martha Bulyk (Harvard University) will report on innovative high-throughput approaches to understanding the gene regulatory network in quantitative terms, such as interaction affinities between DNA binding proteins and their diverse cognate sequences.

Networks and time 

The second session will highlight recent studies of kinetically controlled network behavior. Peter Sorger (Massachusetts Institute of Technology/Harvard University) will discuss insights gained from quantitatively measuring and modeling the activities of signal transducers that respond to death-inducing stimuli.

Alexander Hoffmann (University of California, San Diego) will report on recent work in applying parallel and experimental and kinetic modeling studies to the pathogen-responsive signal regulatory network and gene regulatory network to develop a “virtual cell” capable of predicting responses to pathogen exposure.

Karla Neugebauer (Max Planck Institute of Molecular Cell Biology and Genetics in Dresden) will address the role of kinetics in cotranscriptional splicing as a means to regulate the generation of alternate mature mRNAs. Thus, a key step in regulating gene expression may be understood only by integrating the biochemical processes of transcription and splicing that were previously studied separately.

Networks and space 

The third session will focus on how signal-transduction networks give rise to behaviors in both space and time. Lani Wu (University of Texas Southwestern Medical Center at Dallas) will address the question of how human neutrophils rapidly respond to environmental changes yet ignore irrelevant fluctuations.

Orion Weiner (University of California, San Francisco) will discuss signal-transduction networks in chemotaxing neutrophils and how altering cell geometries can help to identify or rule out mechanisms underlying spatial organization of the signaling components.

Victor Sourjik (Ruprecht-Karls-Universitat Heidelberg) will discuss the assembly and dynamics of signal processing complexes used by bacteria to extract and respond to weak signals from noisy environments.

Networks and noise 

The final session will focus on core design principles by which biological networks can reliably give rise to cellular behaviors despite – or because of – the presence of biochemical noise. Steve Altschuler (University of Texas Southwestern Medical Center at Dallas) will discuss how simple positive feedback circuits that lie at the heart of many pattern-forming networks can make use of biochemical noise to create cell polarity and how noise can be used as a biomarker to discriminate different mechanisms of redundancy in protein interaction networks.

Jeff Hasty (University of California, San Diego) will describe how synthetically designed biological circuits, lab-on-a-chip microfluidic devices and mathematical modeling can be brought together to understand the complexities of gene-regulatory networks in single cells.

Chris Voigt (Massachusetts Institute of Technology) will present recent work on developing a platform for designing biological networks that enable cells to be programmed to perform reliably complex, coordinated tasks.

Meetings_Systems_Biology_AltschulerMeetings_Systems_Biology_HoffmannSteven Altschuler ( is an associate professor at the University of Texas Southwestern Medical Center at Dallas. Alexander Hoffmann ( is a professor at the University of California, San Diego. 

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