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Looking Ahead: What’s Next for the Protein Sciences?

Looking Ahead: What’s Next for the Protein Sciences?. David Wishart, University of Alberta & National Institute of Nanotechnology (NINT) CPI07 Ottawa, June 17, 2007. Outline. Trends in protein science & proteomics What’s next for protein technologies? What’s next for protein engineering

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Looking Ahead: What’s Next for the Protein Sciences?

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  1. Looking Ahead: What’s Next for the Protein Sciences? David Wishart, University of Alberta & National Institute of Nanotechnology (NINT) CPI07 Ottawa, June 17, 2007

  2. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

  3. History of Medicine • 2000 BC - Here, eat this root • 1000 AD - That root is heathen. Here, say this prayer • 1850 AD - That prayer is superstitious. Here, try this potion • 1940 AD - That potion is snake oil. Here, try this antibiotic • 2007 AD - That antibiotic is artificial. Here, eat this root

  4. History of Protein Science • 1970 AD - What does this protein do? • 1980 AD - I don’t care what it does, what is its sequence? • 1990 AD - Don’t just sequence 1 protein, try sequencing all of them • 2000 AD - I don’t care about their sequences, tell me what they interact with • 2007 AD - That’s too much data, what does this protein do?

  5. Science is Cyclic Protein Chemistry Structural Biology Enzymology Systems Biology Structural Genomics Proteomics

  6. Scientists Don’t Like Boundaries 2000 2007 Meta bolomics Systems Biology Proteomics Genomics

  7. 1990 1995 2000 2005 2010 2015 2020 The Future of “Omics” Science? Genomics Proteomics Systems Biology

  8. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

  9. What Are Today’s Technologies? • UPLC, HPLC • CE/microfluidics • LC-MS • FT-MS • QqQ-MS • NMR spectroscopy • X-ray crystallography • Electron microscopy • Fluorescence microscopy Big & Expensive

  10. Miniaturization Revolutionized Genomics

  11. Miniaturization Revolutionized Sequencing

  12. Can It Do The Same For Proteomics? Small & Cheap

  13. HPLC on a Chip

  14. Lab-on-a-Chip

  15. Mass Spectrometer on a Chip

  16. Protein Chips Antibody Array Antigen Array Ligand Array Detection by: SELDI MS, fluorescence, SPR, electrochemical, radioactivity, microcantelever

  17. Technology is Cyclic Too…

  18. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

  19. 1990 1995 2000 2005 2010 2015 2020 The Future of Protein Engineering? Protein Engineering Nanobiotech Synthetic Biology

  20. Proteins Are Nature’s NanoMachines

  21. Nature’s Nanomotor

  22. Nature’s Nano-Stepper Motor

  23. Nature’s Nanocopier

  24. Nature’s NanoFuel Cell

  25. Nature’s Nanosyringe

  26. The Nanobiotech Challenge: • To do what nature has done, using our own design templates

  27. Hybrid Nanomotors C. Montemagno http://www.biomotors.ucla.edu/

  28. Synthetic Biology • Next step beyond Nanobiotech • Point is to assemble functioning systems, not just simple parts • To do in biology what synthetic chemists have done for ~100 years

  29. Synthetic Biology - Making Life? 2004 2006 2008? Synthetic Polio Virus Synthetic 1918 flu Virus Synthetic Mycoplasma

  30. The Ultimate Goal? The Bacterial Nanobot

  31. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

  32. 1990 1995 2000 2005 2010 2015 2020 The Future of Structural Biology Structural Biology “Automated” SB Predictive SB

  33. History of Structural Biology • 1930 AD - This structure will occupy your entire career • 1980 AD - This structure will be your PhD thesis • 1990 AD - This structure will be your MSc thesis • 2000 AD - This structure will be your summer project • 2007 AD - Can I have the structure tomorrow?

  34. Robotic Crystallization

  35. Automated Structure Generation

  36. Trends in Structural Biology # Structures solved % Structures published 1960 1970 1980 1990 2000 2010

  37. Trends in DNA Sequencing # Bases sequenced % Sequnces published 1960 1970 1980 1990 2000 2010

  38. The Protein Fold Universeis Finite All Folds Solved By…? 2010? 2015? 2020? 8 ?

  39. Predicting Protein Structure Rosetta - David Baker, 2001

  40. Tasser - Proteome-wide Prediction Jeffrey Skolnick - 2007

  41. The Synchrotron of Tomorrow? 2006 2016?

  42. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

  43. A Fundamental Difference • What happens if I drop this ball? • Physics -- predictive • What happens if I mix this acid with that base? • Chemistry -- predictive • What happens if this TGF receptor is phosphorylated? • Biology -- observational

  44. THE Grand Challenge… • Making Biology A Predictive Science

  45. What’s it good for? • Basic Science/”Understanding Life” • Predicting Phenotype from Genotype • Understanding/Predicting Metabolism • Understanding Cellular Networks • Understanding Cell-Cell Communication • Understanding Pathogenicity/Toxicity • “Raising the Bar” for Biologists Making Biology a Predictive Science

  46. Are We Ready? • 100’s of completed genomes • 1000’s of known reactions • 10,000’s of known 3D structures • 100,000’s of protein-ligand interactions • 1,000,000’s of known proteins & enzymes • Decades of biological/chemical know-how • Computational & Mathematical resources

  47. The Stamp Collecting Phase of Biology is Almost Over

  48. 1990 1995 2000 2005 2010 2015 2020 The Future of Bioinformatics? Classical Bioinformatics Biosimulation Predictive Biology

  49. Biosimulation - How to Do it?Three Types of Simulation Meso Scale 1.0 - 10 nm Interaction data Kon, Koff, Kd 10 ns - 10 ms Mesodynamics Continuum Model 10 - 100 nm Concentrations Diffusion rates 10 ms - 1000 s Fluid dynamics Atomic Scale 0.1 - 1.0 nm Coordinate data Dynamic data 0.1 - 10 ns Molecular dynamics

  50. Outline • Trends in protein science & proteomics • What’s next for protein technologies? • What’s next for protein engineering • What’s next for structural biology? • What’s next for bioinformatics? • Some closing thoughts

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