Retreat Overview

The Systems Biology Initiative of the West Virginia University Research Corporation held a planning and collaborative interactions retreat at Stonewall Jackson Resort in Roanoke, West Virginia on August 10-11, 2004.

The program began with Dr. John Barnett, Director of WVU Systems Biology, introducing Dr. John Weete, Executive Director of the WVU Research Corporation. Dr. Weete provided the opening remarks whereby he reviewed the on going initiatives, including the Systems Biology, of the Research Corporation to build additional research capability. He discussed the research park plans (generally).

Dr. Weete's Powerpoint Presentation

Dr. Barnett proceeded to acknowledge the WVU Research Corporation for its support and the West Virginia University Colleges of Arts & Sciences, Agricultural and Consumer Sciences, Robert C. Byrd Health Sciences Center and the College of Engineering and Mineral Resources. He also acknowledged General Electric Healthcare Bio-sciences (Formerly Amersham Biosciences).

Dr. Barnett was followed by Dr. Ravi Iyengar the keynote speaker from the Department of Pharmacology and Biological Chemistry at Mount Sinai School of Medicine. Dr. Iyengar presented:
Towards Predictive Models of a Mammalian Cell
Abstract:
The mammalian cell can be thought of as a complex regulatory network that is comprised of a central signal network that interacts with and regulates multiple cellular machines that are responsible for phenotypic behavior. Information flow through the central signaling network is triggered by extra-cellular signals such as hormones binding to their receptors. As information flows through the pathways intracellular signaling pathways interact with one another to form networks. Such networking results in the appearance of regulatory motifs that can lead to information consolidation and consequently to the ability to evoke biological responses. We have analyzed a meso-scale network representing a neuron using graph–theory approaches. Results from these analyses will be presented. We have also analyzed the dynamics of smaller networks by biochemical computation using both standard ordinary differential equation models as well as partial differential equation models incorporating spatially realistic constraints. Such analysis highlights interesting features of signaling networks. These include the ability to form concentrated microdomains of signaling molecules and the regulation of these microdomains by both cellular organelles as well as negative regulators. The physiological consequences of these types of spatial regulation and their implications for developing realistic models of mammalian cell will be discussed.

Bhalla U. S. , Iyengar R (1999) Emergent Properties of Networks of Biological Signaling Pathways Science 283: 381-387

Jordan J. D.,Landau E. M., Iyengar R (2000) Signaling Networks: The Origins of Cellular Multitasking Cell 103: 193-201

Bhalla, U. S., Ram P. T. , Iyengar R (2002) MAP_kinase phospharase as aLocus of Flexibility in a MAP-kinase Signaling Network Science 297:1018-1023

Dr. Boris Knolodenko
Thomas Jefferson University

Temporal and Spatial Control of Receptor Tyrosine Kinase Signaling

Dr. Fei Hua
MIT
Presents
Analysis of Fas Signaling Networks in T cells Using Integrated Experimental and Computational Approaches
Abstract:
Programmed cell death or apoptosis is a critical process for the normal development and function of immune system. Fas (CD95/Apo-1) receptor is an important trigger for apoptosis, and defects in this receptor can lead to the development of autoimmune diseases and cancers of the immune system. Sensitivity to Fas-mediated apoptosis is highly regulated in T lymphocytes and these cells can utilize two distinct Fas signaling pathways, called type I and type II. We have used a combination of experimental and computational strategies to address at a molecular level how T cells regulate their sensitivity to Fas and how different pathways become dominant in these cells. To enable this study, a detailed ordinary differential equation (ODE)-based model for Fas signaling was developed, and a reduced ODE model in which many molecules and parameters are aggregated was derivatized from this detailed model. Both models were trained on a set of experimental data characterizing the kinetics of Fas signaling in T cells, and subsequently used to explore Fas signaling in these cells. Various approaches, such as parametric analysis and hierarchical clustering were used for model study. Some predictions about the behavior of Fas signaling generated by the model were tested by genetically modulating protein expression levels in T cells. Our study provides the understanding that an integrated activity of multiple molecules determines the behavior of Fas signaling. The approach we have taken should be applicable to other signaling pathways and cellular behaviors.

Dr. Pedro Mendes
Research Associate Professor
Virginia Bioinformatics Institute, Virginia Tech
Presents
"Modeling of biochemical networks in the context of systems biology"
Abstract
"Systems biology is an approach that emphasizes the global properties of living systems rather than the properties of purified biological molecules. Two major components of systems biology are

(1) large-scale profiling experiments, providing 'snapshots' of the state of the cells, and

(2) models of biological networks. The latter are important to provide context and to rationalize the experimental results. Properly validated models are also useful to predict properties of biological systems, often in ways that would be impossible by experiment. In essence, models are expressions of the existing knowledge about biological systems. Methods to construct and validate computational models of biological systems will be discussed, together with practical examples using software developed in my laboratory."

Dr. Barnett concluded the morning session by announcing that Systems Biology would be sponsoring four pilot studies.

Three team building groups were formed. System biology approaches to cancer prevention and cure chaired by Dr. Eddie Reed-Director, WVU Mary Babb Randolph Cancer Center.

System Biology approaches to toxicology of mixtures/environmental problems chaired by Dr. John Barnett, Director-WVU Systems Biology

System biology approaches to Neurosciences chaired by Dr. Robert Goodman, Chairman-WVU Department of Physiology & Pharmacology

The morning of August 11th began with Dr. David Morrison of Grant Writer's Seminars and Workshops, conducting a half day workshop on "Write Winning Grants"

He was followed by Dr. Steve Armentrout, President & CEO of Parabon Computation presenting information on the West Virginia Computer Grid

Two additional workshops followed in the afternoon, Dr. Chris Cox from the University of Tennessee presenting BioSPICE software and Dr. Timothy Vincent, West Virginia University conducting a workshop on Proteomics

Systems Biology Retreat Photo Gallery