C70 NATURE| VOL 402 | SUPP| 2 DECEMBER 1999 | www.nature.com

Going for grand challenges

If scientists have access to supercomputing power from their desktops through the Internet by 2010, it will allow them to take on much more ambitious research challenges. "I think we will have the kind of computing power and tools to build models of whole cells and organisms," says Van Houweling, "but these new tools that we are talking about are becoming available only now to ordinary scientists."

Most biologists at present are happy to look for the homologue of the particular gene or protein sequences they are interested in. But by using more powerful computers, it will be possible to start looking at the integration of information across the genome. "If we hope to understand biology, instead of looking at one little protein at a time, which is not how biology works, we will need to understand the integration of thousands of proteins in a dynamically changing environment," says Venter. This is the direction Celera will take next year once it has completed the sequencing of the human and mouse genomes. To do so, the company is building what will be the world's largest supercomputer for biology, a 1,200-processor machine. "A computer will be the biologist's number one tool," predicts Venter. "The data sets are beyond the capacity of the human brain."

A pointer as to where computational biology is likely to go is a software package called E-cell, developed by Masaru Tomita from Keio University in Japan. The package, which can be downloaded from his website at http://www.e-cell.org, simulates basic cellular processes. Tomita has just completed a model of human erythrocytes and is building other models of human mitochondria, signal transduction for chemotaxis in the bacterium Escherichia coli, and gene expression networks in this bacterium's lactose operon (a collection of genes that are switched on when the bacterium is forced to feed on lactose sugar). Nourished properly, the "Tamagotchi" erythrocyte reaches a steady state where metabolite concentrations com-pare well with those reported in real mammalian erythrocytes. Tomita is now inhibiting enzymes from the glycolytic pathway in silico, such as hexokinase, glucose-6-phosphate dehydrogenase, phosphofructokinase and pyruvate kinase, in a bid to throw light on the cellular metabolism of people suffering from hereditary anaemia, which is caused by deficiencies of these enzymes. Many are predicting that the fruitfly Drosophila will be the main target for complex computer modelling in developmental biology. Its genome will soon be available, and many hands make light work; there are some 6,000 Drosophila researchers out there.

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