Genomes To Life

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

2. 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 www.genomes-to-life.org

3. DOE Genomes to Life Program 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 Math Computer Science Biology Genomics proteomics GTL

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

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

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

7. Biology for the 21st Century 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 Models and simulations Annotated data sets Raw data sets

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

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

10. Payoffs in the mid to long term Clean, efficient biological alternative to fossil fuels Enable independence of foreign oil Harnessing metabolic pathways/mechanisms in H2-producing microbes Designer plants for easily convertible biomass for fuels, chemical feed stocks, products Understanding metabolic pathways and networks, and cell wall synthesis Stabilize atmospheric carbon dioxide to counter global warming Investigating enzymes, regulation, environmental cues, and effects Strategies and methods for storing and monitoring carbon

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