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Center for Systems Biology

The Center's Goals

The Chicago Center for Systems Biology will study the dynamics of transcriptional networks in physiological, developmental and evolutionary time scales. Most experimental studies to date have focused on mapping transcriptional regulatory network topologies.  We propose to go beyond mapping topologies to develop models of behavior of transcriptional regulatory networks during physiological stress, during cellular and organismal development, and during the evolution of species.  The scientific aim of the Center is to uncover the organizational principles that transcriptional regulatory networks share as they respond to physiological, development and evolutionary inputs and pressures, while also determining the extent to which each type of network we will study is unique. The training, education and outreach aim of the Center is to establish programs for teaching Systems Biology from grade school to graduate school, and to promote and enable interdisciplinary Systems Biology research for investigators at the three CBC institutions.

Research Projects

There will be five inter-related core projects (see below) that we will examine and compare both the structure and dynamics of a series of different transcriptional regulatory networks. Modeling and experimentation on complex transcriptional network responses to environmental stresses, and an examination of the evolution of transcriptional networks will be important components of the proposed studies. Building on an understanding of basic network responses to environmental perturbations we will then examine transcriptional networks that are "designed" to integrate information from complex signaling environments in a developmental context. Systematic data collection, modeling, prediction, and hypothesis testing will represent the four phases of each core project. There will be feedback among the phases so that each guides the other. Each core project will provide both unique and common perspectives on how transcriptional networks respond to changing environments.

Core Projects

  • Transcriptional dynamics that control single cell behavior in response to stress in bacteria. The most primitive stress response networks will be examined (P Cluzel, UC, Leader; A Rzhetsky, UC, Co-Leader).
  • Transcriptional dynamics of the stress response system itself in key model organisms. Yeast, C. elegans and Drosophila models will be examined to determine the primordial metazoan stress response circuits (R Morimoto, NWU, Leader; I Ruvinsky, UC, Co-Leader; L Amaral, NWU, Co-Leader).
  • Transcriptional dynamics and functional evolution of the Drosophila segmentation network. Stability and flexibility of this network will be examined under physiological stress conditions using a novel microfluidics system. The evolutionary dynamics of the network flexibility will be examined through both comparative and experimental approaches. Emphasis will be placed on understanding features of the segmentation pathway that contribute a robust segmentation phenotype in the face of challenges imposed by the environment and mutation (K White, UC, Leader; M Kreitman, UC, Co-Leader; R Ismagilov, UC, Co-Leader).
  • Transcriptional dynamics of the developing Drosophila eye. As a model for development of two different cell types in a field of cells we will examine the networks that drive the choice between differentiation between R7 and cone cell fates. The network will be examined as cellular differentiation happens in space and time in a dynamically changing cellular environment (I Rebay, UC, Leader; R Carthew, NWU, Co-Leader).
  • Transcriptional control of hematopoietic stem cell differentiation in mammals. The microenvironment of differentiating stem cells is key in determining their differentiation patterns. This system will be examined as an example of a complex set of cellular differentiation decisions in a changing signaling environment (H Singh, UC, Leader; J Crispino, NWU, Co-Leader; A Dinner, UC, Co-Leader).

The core projects are designed to analyze the structure and function of increasingly complex transcriptional regulatory networks that respond to environmental cues. Our studies are designed to examine the dynamics of transcriptional networks on physiological, developmental and evolutionary time scales. Successful execution of the core projects will be made possible through the establishment of a "core" infrastructure, providing data-gathering and databasing technology, as well as computational and theoretical modeling expertise, to be shared among the projects. The common representation of data for all projects and shared approaches to modeling link the projects intellectually, thus promoting the synergism required to achieve the overarching scientific aims of the proposal.