Gene Network Sciences and UCSD Researchers Discover Connection Between Metabolic Pathways and Cancer

Results Published in Molecular Systems Biology

CAMBRIDGE, Mass., February 15, 2007 /PRNewswire/ -- The most recent edition of Molecular Systems Biology (a Nature publication), released this week, contains the results of a study discovering a "missing link" between metabolic pathways and cell reproduction. The publication, co-authored by researchers at Gene Network Sciences, Inc. (GNS) and the Howard Hughes Medical Institute and Department of Cellular and Molecular Medicine at the University of California San Diego (UCSD) School of Medicine, details how this missing link could become a key target in a new class of cancer drugs used to halt cancer cell replication and tumor growth. Entitled "A Systems Biology Dynamical Model of Mammalian G1 Cell Cycle Progression," the paper describes the combined experimental and computational approach that the GNS-UCSD team used to better understand a complex process relevant to cancer biology: progression of the mammalian G1 cell cycle, one of the phases in mammalian cell reproduction and tumor growth.

GNS and UCSD researchers used GNS software to create a quantitative computer model that accurately simulates G1 cell cycle progression, is capable of reproducing observations from in vitro cell culture studies, and serves as a foundation for the development of new cancer drugs targeting G1 cell cycle progression. Specifically, the researchers used the quantitative reverse- engineering and modeling approach reflected in the GNS software platform to predict the presence of a previously unidentified "modifier" that is postulated to cause transition of the cell cycle from the growth-factor dependent Early G1 phase to the growth-factor independent Late G1 phase.

"This is the first time that quantitative evidence has pointed to the necessary existence of a key metabolic factor controlling passage through the restriction point in the cell cycle that commits the cell to DNA replication. The combined efforts of our lab and the GNS team and their software has allowed us to probe further into the inner workings of cell replication and the origins of cancerous cell growth," said Dr. Steve Dowdy, the principal UCSD investigator in the collaboration and Howard Hughes Medical Institute researcher. Dr. Dowdy's lab focuses on understanding the molecular basis of cell cycle progression and deregulation, and developing novel macromolecular anticancer therapeutics.

The GNS software used in the GNS/UCSD collaboration enables the creation of quantitative models that can reflect the causal connections between drugs, genes, proteins, covariate data, and biological endpoints. These models are reverse-engineered directly from 'omics data such as SNP, gene expression, proteomics, and metabolomics data combined with clinical or pre-clinical endpoints and then simulated using GNS software.

"The UCSD team generated key experimental data that was used in the GNS software to identify a novel potential intervention target in cancer. We hope this discovery will open up a new avenue in cancer biology research and will someday lead to new drugs that can stop the growth of tumors and spread of cancer," said Dr. Iya Khalil, executive vice president of GNS and the company's lead scientist in the collaboration.

About Gene Network Sciences

Founded in 2000, Gene Network Sciences (www.gnsbiotech.com) is a privately held biosimulation company with offices in Cambridge, Massachusetts, and Ithaca, New York. GNS technology rapidly turns complex and heterogeneous data sets into cell and organ-level computer models able to simulate the clinical performance of drugs and drug candidates. By discovering how and why specific drug candidates impact human biology, GNS technology increases the confidence in moving drug candidates forward and ultimately improves clinical trial success rates. GNS provides drug development services to pharmaceutical customers using its proprietary software platform, which includes the patented Diagrammatic Cell Language(TM), VisualCell(TM), DigitalCell(TM), VisualHeart(TM), DigitalHeart(TM), NI Engine(TM), and PerMDE(TM) diagnostic engine.

About UCSD

The Howard Hughes Medical Institute at UCSD School of Medicine in La Jolla, California, represents one of the three premiere places to do biomedical science in the United States. Dr. Dowdy's lab is uniquely situated and equipped to uncover physiologic regulators of G1 cell cycle progression.

CONTACT: Debbie Pfeifer of Gene Network Sciences, +1-206-282-5098, or debbie@gnsbiotech.com

Web site: http://gnsbiotech.com/

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Posted: February 2007

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