looking ahead: what’s next for the protein sciences? david wishart, university of alberta &...
TRANSCRIPT
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Looking Ahead: What’s Next for the Protein Sciences?
David Wishart, University of Alberta & National Institute of
Nanotechnology (NINT)CPI07 Ottawa, June 17, 2007
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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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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
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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?
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Science is Cyclic
ProteinChemistry
Proteomics
StructuralBiology
StructuralGenomics
Enzymology
SystemsBiology
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Scientists Don’t Like Boundaries
GenomicsGenomics
ProteomicsProteomics
Metabolomics
SystemsSystemsBiologyBiology
2000 2007
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The Future of “Omics” Science?
1990 1995 2000 2005 2010 2015 2020
Genomics
Proteomics
Systems Biology
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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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What Are Today’s Technologies?
• UPLC, HPLC• CE/microfluidics• LC-MS• FT-MS• QqQ-MS• NMR spectroscopy• X-ray crystallography• Electron microscopy• Fluorescence
microscopyBig & Expensive
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Miniaturization Revolutionized Genomics
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Miniaturization Revolutionized Sequencing
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Can It Do The Same For Proteomics?
Small & Cheap
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HPLC on a Chip
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Lab-on-a-Chip
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Mass Spectrometer on a Chip
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Protein Chips
Antibody Array Antigen Array Ligand Array
Detection by: SELDI MS, fluorescence, SPR, electrochemical, radioactivity, microcantelever
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Technology is Cyclic Too…
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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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The Future of Protein Engineering?
1990 1995 2000 2005 2010 2015 2020
Protein Engineering
Nanobiotech
Synthetic Biology
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Proteins Are Nature’s NanoMachines
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Nature’s Nanomotor
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Nature’s Nano-Stepper Motor
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Nature’s Nanocopier
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Nature’s NanoFuel Cell
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Nature’s Nanosyringe
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The Nanobiotech Challenge:
• To do what nature has done, using our own design templates
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Hybrid Nanomotors
http://www.biomotors.ucla.edu/
C. Montemagno
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Synthetic Biology
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• 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
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Synthetic Biology - Making Life?
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SyntheticPolio Virus
Synthetic1918 flu
Virus
SyntheticMycoplasma
2004 2006 2008?
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The Ultimate Goal?
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The Bacterial Nanobot
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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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The Future of Structural Biology
1990 1995 2000 2005 2010 2015 2020
Structural Biology
“Automated” SB
Predictive SB
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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?
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Robotic Crystallization
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Automated Structure Generation
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Trends in Structural Biology
1960 1970 1980 1990 2000 2010
% S
truc
ture
s pu
blis
hed
# S
truc
ture
s so
lved
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Trends in DNA Sequencing
1960 1970 1980 1990 2000 2010
% S
equn
ces
publ
ishe
d
# B
ases
seq
uenc
ed
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The Protein Fold Universeis Finite
All FoldsSolvedBy…?
2010?
2015?
2020?
8 ?
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Predicting Protein Structure
Rosetta - David Baker, 2001
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Tasser - Proteome-wide Prediction
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Jeffrey Skolnick - 2007
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The Synchrotron of Tomorrow?
2006 2016?
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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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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
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THE Grand Challenge…
• Making Biology A Predictive Science
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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
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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
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The Stamp Collecting Phase of Biology is Almost Over
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The Future of Bioinformatics?
1990 1995 2000 2005 2010 2015 2020
Classical Bioinformatics
Biosimulation
Predictive Biology
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Biosimulation - How to Do it?Three Types of Simulation
Atomic Scale0.1 - 1.0 nmCoordinate dataDynamic data0.1 - 10 nsMolecular dynamics
Meso Scale1.0 - 10 nmInteraction dataKon, Koff, Kd10 ns - 10 msMesodynamics
Continuum Model10 - 100 nmConcentrationsDiffusion rates10 ms - 1000 sFluid dynamics
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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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Innovation & The Roller Coaster of Expectations
Time
Exp
ecta
tions
TechnologyTrigger
The “Hillof Hype”
Peak ofExcitement
Descent of Disillusionment
Valley ofdespair
Plateau ofPerformance
Road toRespectability
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Omics Rides on The Roller Coaster of Expectations
Time
Exp
ecta
tions
TechnologyTrigger
The “Hillof Hype”
Peak ofExcitement
Valley ofdespair
Plateau ofPerformance
Sys
tem
sB
iolo
gy
Met
abol
omic
s
Pro
teo
mic
s Tra
nscr
ipto
mic
s
Gen
omic
s
Road toRespectability
Descent of Disillusionment
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Science Funding Rides on The Roller Coaster of Expectations
Time
Exp
ecta
tions
TechnologyTrigger
The “Hillof Hype”
Peak ofExcitement
Valley ofdespair
Plateau ofPerformance
Road toRespectability
Descent of Disillusionment
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Student Enrollment and Staff Recruitment Rides on The Roller Coaster
of Expectations
Time
Exp
ecta
tions
TechnologyTrigger
The “Hillof Hype”
Peak ofExcitement
Valley ofdespair
Plateau ofPerformance
Road toRespectability
Descent of Disillusionment
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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
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Thanks
Past and present members ofmy laboratory, PENCE, GenomeCanada and the CPI organization
It’s been a good 7 years!