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February 11, 2003

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   Denine Hagen, (858) 534-2920 or


A team of bioengineers has created the first computer model that simulates gene function and cellular metabolism in yeast (Saccharomyces cerevisiae), an organism that is at the center of modern biology. The model integrates the worldwide body of knowledge about this single-cell organism into a mathematical model capable of simulating 1,175 reactions produced by 708 genes interacting with 723 metabolites. It is the first predictive genome-scale model for a eukaryotic cell, and brings researchers one step closer to using computer simulations to aid in drug discovery.

The model was created by bioengineers at the University of California, San Diego (UCSD) Jacobs School of Engineering and the Technical University of Denmark. Results are published in the February 2003 issue of Genome Research.

“Now that we have created an in silico model for an organism that is used to study many disease conditions, we are getting closer to applying our work towards finding treatments for human disease,” said Bernhard Palsson, professor of bioengineering at the UCSD Jacobs School, and a co-author on the study.

Yeast is a single-cell eukaryotic organism, meaning that its DNA is contained in a nucleus. Because its internal signaling pathways are similar to those of human cells, it is widely used as a testbed for discovering new knowledge about cell biology. Scientists also use yeast to study human disease, particularly cancers and inherited metabolic diseases. In commercial settings, yeast is used to make foods and commodity chemicals.

The process of reconstructing how the network of genes and gene products interact in yeast, was a laborious, time-consuming task. A team of six researchers gathered information from databases, books and publications in scientific journals. When conflicts between published data appeared, the researchers manually selected the information that was more likely to be true. They then began creating mathematical equations that described specific gene functions and reactions, and combined the equations into one model.

The researchers are diligently developing the model to simulate and predict the behavior of yeast, and early results show the model is correct more than 70 percent of the time.

“The real excitement for us is the failures. When the model is wrong, it points to gaps in our knowledge about yeast metabolism and may guide us to experiments that can be done to fill in the gaps,” said Palsson.

The team is continuing to revise their model and hopes to complete a second version within a few months. Collaborators include Palsson, director of the Genetic Circuits Laboratory at UCSD Jacobs School; Jens Nielsen, director of the Center for Process Biotechnology at the Technical University of Denmark; Jochen Forster at the Technical University of Denmark; UCSD bioengineering Ph.D. candidate Iman Famili; and post-doctoral researcher Patrick Fu.

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