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 What’s next for structural biology? What’s next for bioinformatics? Some closing thoughts

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

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?

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

Scientists Don’t Like Boundaries Genomics Proteomics Meta bolomics SystemsBiology

The Future of “Omics” Science? Genomics Proteomics Systems Biology

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

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

Miniaturization Revolutionized Genomics

Miniaturization Revolutionized Sequencing

Can It Do The Same For Proteomics? Small & Cheap

HPLC on a Chip

Lab-on-a-Chip

Mass Spectrometer on a Chip

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

Technology is Cyclic Too…

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

The Future of Protein Engineering? Protein Engineering Nanobiotech Synthetic Biology

Proteins Are Nature’s NanoMachines

Nature’s Nanomotor

Nature’s Nano-Stepper Motor

Nature’s Nanocopier

Nature’s NanoFuel Cell

Nature’s Nanosyringe

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

Hybrid Nanomotors C. Montemagno

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

Synthetic Biology - Making Life? Synthetic Polio Virus Synthetic 1918 flu Virus Synthetic Mycoplasma ?

The Ultimate Goal? The Bacterial Nanobot

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

The Future of Structural Biology Structural Biology “Automated” SB Predictive SB

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?

Robotic Crystallization

Automated Structure Generation

Trends in Structural Biology % Structures published # Structures solved

Trends in DNA Sequencing % Sequnces published # Bases sequenced

The Protein Fold Universe is Finite All Folds Solved By…? 2010? 2015? 2020? 8 ?

Predicting Protein Structure Rosetta - David Baker, 2001

Tasser - Proteome-wide Prediction Jeffrey Skolnick

The Synchrotron of Tomorrow? ?

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

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

THE Grand Challenge… Making Biology A Predictive Science

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

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

The Stamp Collecting Phase of Biology is Almost Over

The Future of Bioinformatics? Classical Bioinformatics Biosimulation Predictive Biology

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

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

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

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

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

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

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

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