1. Genomes To Life Biology for 21 st Century A Joint Initiative of the Office of Advanced Scientific Computing Research and Office of Biological and Environmental Research http://DOEGenomesToLife.org Al Geist December 2, 2003 RAM Workshop Oak Ridge, TN

2. www.genomes-to-life.org Human Genome Project Determine the Entire DNA Sequence for Humans New computational tools was key to the success All life—plants, animals, insects, and microbes are defined by their genome, which is a long string of four nucleotides A, C, G, T Human –24 chromosomes contain 6 ft of DNA –3 billion nucleotides –35,000 genes –Only 0.0001% difference between people –Differ by 2 million nucleotides Hundreds of genomes have now been done (Bug a month) Book of life has 4 letters, words are genes, sentences are machines and regulators. The next step is to determine the sentences

3. Understand how genes, proteins, and cells work in intricate networks to form dynamic living systems exquisitely responsive to their environment. Start with simple life form – single cell organism Discover how microbial genes, proteins and cells work together Use supercomputers to analyze data, predict, model, and simulate how protein machines interact through complex interconnected pathways DOE Genomes to Life Program Biology Genomics proteomics Math Computer Science GTL

4. Molecular Machines Microbial Communities Regulatory Pathways Develop the computational methods and capabilities to advance understanding of complex biological systems Four Research Areas of Genomes to Life Understanding the essential processes of living systems

5. www.genomes-to-life.org Molecular Machines Fill Cells Many interlinked proteins form interacting machines From The Machinery of Life, David S. Goodsell, Springer-Verlag, New York, 1993.

6. www.genomes-to-life.org Regulatory Networks Control the Machines Gene regulation controls what genes are expressed Proteome changes over time and due to environmental conditions

7. Biology is undergoing a major transformation that will be enabled and ultimately driven by computations Swimming in Data: Exploding Need to Capture and Manipulate Data GTL Knowledge Base: Integration of Large Datasets to do Predictive Modeling Annotated data sets Raw data sets Biology for the 21 st Century Models and simulations

8. www.genomes-to-life.org Broad Scale of Biological Complexity and Computational Requirements

9. Understanding metabolic pathways and mechanisms of native microbes Bioremediation methods for accelerated and less costly cleanup strategies Understanding responses of metabolic and regulatory pathways of organisms to environmental conditions Improved diagnostics and standards for ecological and human health Investigating protein expression patterns, protein-protein interactions, and molecular machines Sensors for detecting pathogens and toxins; strategies to enable strain identification; and improved vaccines and therapeutics for combating infectious disease Payoffs in the near term Significant savings in toxic waste cleanup and disposal Technologies and systems for detecting and responding to biological terrorism Improve the scientific basis for worker health and safety

10. Payoffs in the mid to long term Harnessing metabolic pathways/mechanism s in H 2 -producing microbes Clean, efficient biological alternative to fossil fuels Enable independence of foreign oil Understanding metabolic pathways and networks, and cell wall synthesis Designer plants for easily convertible biomass for fuels, chemical feed stocks, products Strategies and methods for storing and monitoring carbon Stabilize atmospheric carbon dioxide to counter global warming Investigating enzymes, regulation, environmental cues, and effects

11. Simulation & Modeling Tools for Ease of Use Supercomputer Resources High throughput Experiments ? Biology community Distributed Databases Human Health Protection Energy Security Energy Cleanup GenesPathwaysProteins RACHET Advanced Computational Algorithms Integrated Cyclic Process