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 Proteomics Structural Biology Structural Genomics Enzymology Systems Biology

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

7. The Future of “Omics” Science? 1990 1995 2000 2005 2010 2015 2020 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. The Future of Protein Engineering? 1990 1995 2000 2005 2010 2015 2020 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 http://www.biomotors.ucla.edu/ C. Montemagno

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? Synthetic Polio Virus Synthetic 1918 flu Virus Synthetic Mycoplasma 2004 2006 2008?

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. The Future of Structural Biology 1990 1995 2000 2005 2010 2015 2020 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 1960 1970 1980 1990 2000 2010 % Structures published # Structures solved

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

38. The Protein Fold Universe is 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. The Future of Bioinformatics? 1990 1995 2000 2005 2010 2015 2020 Classical Bioinformatics Biosimulation Predictive Biology

49. Biosimulation - How to Do it? Three Types of Simulation Atomic Scale 0.1 - 1.0 nm Coordinate data Dynamic data 0.1 - 10 ns Molecular dynamics 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

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

51. Innovation & The Roller Coaster of Expectations Time Expectations Technology Trigger The “Hill of Hype” Peak of Excitement Descent of Disillusionment Valley of despair Plateau of Performance Road to Respectability

52. Omics Rides on The Roller Coaster of Expectations Time Expectations Technology Trigger The “Hill of Hype” Peak of Excitement Valley of despair Plateau of Performance Systems Biology Metabolomics Proteomics Transcriptomics Genomics Road to Respectability Descent of Disillusionment

53. Science Funding Rides on The Roller Coaster of Expectations Time Expectations Technology Trigger The “Hill of Hype” Peak of Excitement Valley of despair Plateau of Performance Road to Respectability Descent of Disillusionment

54. Student Enrollment and Staff Recruitment Rides on The Roller Coaster of Expectations Time Expectations Technology Trigger The “Hill of Hype” Peak of Excitement Valley of despair Plateau of Performance Road to Respectability Descent of Disillusionment

55. Some Final Thoughts The long-term future of protein science is very bright The short-term is still a little rocky Protein scientists need to “create a community” for advocacy, recruitment and funding (BC’s Proteomics Network, CPI --> CPO?) New sources of support need to be found (Less Federal = More Provincial? State?) Future will depend on how well we train and retain the next generation of protein scientists

56. Thanks Past and present members of my laboratory, PENCE, Genome Canada and the CPI organization It’s been a good 7 years!