Nitin S. Baliga Professor

Institute for Systems Biology, Seattle

“Ask not what you can do for evolution,ask what evolution can do for you”

Redirecting Evolution

A salty solution

Biology has much more to offer…

Courtesy: Calvin J. Hamilton

Grand applications

Decoding complexity

Modified from Innovech WordPress

genome… …parts… …circuits

Acquisition of complexity: Conditionally activated control inside genes

Koide, Reiss, et al. (2009) MSB

DNA

RNA

Protein

Metabolites

Phenotype

Genotype

ENVIRONMENT

Genetic information processing is dynamic

Systems Approach:Perturb, Observe and Model

Environmental Perturbations

Phenotypes

Genes/Proteins

Parts of a system

Consequences of small changes resonate

throughout the network

Baliga NS, Science (2008)

Tagkopolous et al., Science (2008)

Constrained Evolution

Barrett et al. PNAS (2005); Baliga NS, Science (2008) ; Tagkopolous et al., Science (2008)

II. Few dominant states

I. Interlocked architecture

Anticipation of linked changes

Whitehead et al., PLoS One (2008); Kaur et al., MSB (2010)

Explosion of technologies

System wide data:looking at the same phenomenon through different lenses

• Concentrations of molecules

– Transcription starts, stops

– mRNA levels

– Protein levels

• Interactions among

molecules

– functional

relationships/associations

(phylogenetic pattern)

– genome organization

(operons, chromosomal

proximity)

• Enzyme reactions

• Modifications of molecules

Reiss et al, BMC Bioinformatics (2006), Bonneau et al., Genome Biology (2006)

Reverse engineering biological circuits

De novo discovery of a subcircuit

Inferelator:Learning regulatory influences

Bonneau et al Genome Biology (2006)

Data-driven discovery of a biological sub-circuit

Bonneau et al, Cell, 2007

Bonneau et al. (2007) Cell; Baliga NS (2008) Science

Predicting new cellular behaviors

Bonneau et al. (2007) Cell; Baliga NS (2008) Science

Traversing scales

Tracking individual cells

0

500

1000

1500

2000

2500

3000

3500

0 500 1000 1500

Time (min)

Me

an

Flu

ore

sce

nce

Copper (via tracer)

Single cell yvgX (via GFP)

0

500

1000

1500

2000

2500

3000

3500

0 500 1000 1500

Time (min)

Me

an

Flu

ore

sce

nce

Tracking individual cells

Copper (via tracer)

Multiple single cells yvgX (via GFP)

Koide, Pang and Baliga,(2009) Nat Rev Micro

Rational Systems Re-engineering

Reengineer circuits

Rich Bonneau, NYU; Marc Facciotti, UC Davis; Paul Shannon, ISB; Vesteinn Thorsson, ISB

Tie Koide, U of Sao Paulo; Amy Schmid, Duke U; Kenia Whitehead Lee Hood, Bill Longabaugh, Jocelyne DiRuggiero, Carl Johnson

John Tainer and MAGGIE investigators

Funding from NSF, NIH, DoE, DoD, Battelle, Luxembourg and NASA

Acknowledgements

http://baliga.systemsbiology.net

Classes of cis-regulatory motifs

6 TBPs

7 TFBs

Acquisition of complexity:I. Gene Family Expansion

Turkarslan et al. in preparation; Facciotti et al., (2007) PNAS

Snapshots of regulons

1 2

3 4

Ensembles of networks

TF1

TF2

TF2

TF3

Snapshots of a regulon

1 2

3 4

Ensemble networks TF1 TF2

crtB1

C