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

• 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

ProteinChemistry

Proteomics

StructuralBiology

StructuralGenomics

Enzymology

SystemsBiology

Scientists Don’t Like Boundaries

GenomicsGenomics

ProteomicsProteomics

Metabolomics

SystemsSystemsBiologyBiology

2000 2007

The Future of “Omics” Science?

1990 1995 2000 2005 2010 2015 2020

Genomics

Proteomics

Systems Biology

Outline







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

http://groningen.bio.ucalgary.ca/bio/img/700.jpg

Miniaturization Revolutionized Genomics

Miniaturization Revolutionized Sequencing

Can It Do The Same For Proteomics?

Small & Cheap

HPLC on a Chip

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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

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Technology is Cyclic Too…



Outline







The Future of Protein Engineering?

1990 1995 2000 2005 2010 2015 2020

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

http://www.biomotors.ucla.edu/

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?


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SyntheticPolio Virus

Synthetic1918 flu

Virus

SyntheticMycoplasma

2004 2006 2008?

The Ultimate Goal?



The Bacterial Nanobot

Outline







The Future of Structural Biology

1990 1995 2000 2005 2010 2015 2020

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

1960 1970 1980 1990 2000 2010

% S

truc

ture

s pu

blis

hed

# S

truc

ture

s so

lved

Trends in DNA Sequencing

1960 1970 1980 1990 2000 2010

% S

equn

ces

publ

ishe

d

# B

ases

seq

uenc

ed

The Protein Fold Universeis Finite

All FoldsSolvedBy…?

2010?

2015?

2020?

8 ?

Predicting Protein Structure

Rosetta - David Baker, 2001

Tasser - Proteome-wide Prediction



Jeffrey Skolnick - 2007

The Synchrotron of Tomorrow?

2006 2016?

Outline







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?

1990 1995 2000 2005 2010 2015 2020

Classical Bioinformatics

Biosimulation

Predictive Biology

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

Outline







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

Omics Rides on The Roller Coaster of Expectations

Time

Exp

ecta

tions

TechnologyTrigger


Peak ofExcitement

Valley ofdespair


Sys

tem

sB

iolo

gy

Met

abol

omic

s

Pro

teo

mic

s Tra

nscr

ipto

mic

s

Gen

omic

s



Science Funding Rides on The Roller Coaster of Expectations

Time

Exp

ecta

tions

TechnologyTrigger


Peak ofExcitement

Valley ofdespair




Student Enrollment and Staff Recruitment Rides on The Roller Coaster

of Expectations

Time

Exp

ecta

tions

TechnologyTrigger


Peak ofExcitement

Valley ofdespair




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 ofmy laboratory, PENCE, GenomeCanada and the CPI organization

It’s been a good 7 years!

http://www.pence.ca/

looking ahead: what’s next for the protein sciences?

Documents

protein technologies

protein engineeringwhats

protein sciences

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