1. Institute for Systems Biology
John Aitchison, Ph.D.
Professor
VP, Director for Integrative Biology

2. Three Pillars of ISB
Systems Biology
Collaborations
Partnerships
Commercial Spinouts
Stewardship
Education

3. Systems Biology
• Different in concept
• Demands cycle of innovation
• Potential to Drive All Biological Research
• New research opportunities
• Medicine – Predictive, Preventive, Personalized
and Participatory – P4 medicine
• Commercial opportunities

4. Biology is a systems problem
• Neutrophil – chasing down
bacteria to eat it
• A system is any collection of interacting parts with
emergent behavior.
• Emergence is when the whole is greater than the sum of
the parts.

5. What is a System?
• A system is any collection of interacting parts with
emergent behavior.
• Emergence is when the whole is greater than the sum of
the parts.

6. What is a System?
• A system is any collection of interacting parts with
emergent behavior.
• Emergence is when the whole is greater than the sum of
the parts.

7. Biological Systems Are Self Organizing
Cells: dynamic networks of interacting components, with
millions of local interactions (systems)

8. Traditional approaches study a single
gene/RNA/protein at a time
DNA RNA Protein
Time
Single gene
But there are tens of thousands of genes/RNA/proteins!

9. Systems Biology
DNA RNA Protein
Driven by
computation
and technology
A holistic view

10. Systems Biology drives a cycle of innovation
Biological
Information
Biology
And Insight
Cross-Disciplinary Systems Biology seeks to
Culture address important and complex
Team Science problems in biology that have
previously been intractable.

11. Systems Biology drives a cycle of innovation
Biology
Cross-Disciplinary
Culture
Team Science

12. Three Major Research Thrusts at ISB
Medical Research Sustainability Health Care
(Global Health) (BioEnergy) (P4 Medicine)
Solving Complex Problems Requires a Systems Approach
ISB is attacking these problems through partnerships.
Drive systems biology and apply in these major areas

13. Three Major Research Thrusts at ISB
Medical Research Sustainability Health Care
(Global Health) (BioEnergy) (P4 Medicine)

14. The fundamental challenge:
How can we understand the emergent macroscopic properties of the
system from its parts and their interactions?
Analogy: circuit diagram

15. Systems Biology and Medicine
Dynamic, Responsive Molecular Networks
• How do perturbations (disease)
propagate through a network?
• How can we alter the network of a
diseased individual and revert it to
‘normal’?

16. Systems biology to understand complex responses
- of cells - and of pathogens and hosts
Stimulus
PROGRAM of response
(fatty acids)
~40% of the genes change in
expression

17. Systems biology to understand complex responses
- of cells - and of pathogens and hosts
Pathogen
PROGRAM of response
(
~40% of the genes change in
expression
~50% of human genes change expression
upon infection with Vaccinia virus
(Grinde et al., J. Virol, 4: 24 2007)

18. Application of systems biology to vaccine
development
To identify predictors of vaccine
immunogenicity (signatures)
To understand the molecular
networks leading to a protective
response
Edward Jenner
1796 To re-engineer the response with
adjuvants

19. ISB-SBRI Partnership

20. ISB-SBRI Partnership
Combine Complementary Strengths
Infectious disease research
Systems biology
Immunology
Technology
Revolutionize scientific approaches to
vaccine and drug development for
global infectious disease
Unique, Creative and Productive Environment
shared facilities,
enhanced scientific exchange
new research opportunities - funding

21. Solving Complex Problems Requires a Systems Approach
Medical Research Sustainability Health Care
(Global Health) (BioEnergy) (P4 Medicine)

23. Solving Complex Problems Requires a Systems Approach
Medical Research Sustainability Health Care
(Global Health) (BioEnergy) (P4 Medicine)

24. Dynamics of a Brain Network in Prion
Neurodegenerative Disease
Prion accumulation network

25. Dynamics of a Brain Network in Prion
Neurodegenerative Disease
Prion accumulation network
300 genes encode the core prion disease response—map to 4 major networks
Network dynamics explains all disease pathophysiology
Profound implications for diagnostics and therapy – P4

26. Predictive, Personalized, Preventive
and Participatory (P4) Medicine
Genome sequence; multiparameter measurements; computation
26

27. P4 Medicine
• Predictive
• Probabilistic health history
• DNA sequence & Regular multi-
parameter (blood) measurements
• Personalized
• Unique individual human genetic
variation mandates individual treatment
• Preventive
• Design of therapeutic and preventive
drugs/vaccines via systems approaches
• Participatory:
• Patient understands and participates in
medical choices

28. P4 Medicine
• Billions of data points for each individual
• Focus on wellness
• Early detection
– Individual is own control (longitudinal data)
• Disease stratification
– Targeted therapies
• Personalized treatments
– Stratified disease and patients – matched with drug
• Monitor Disease progression and therapy
• Assess re-occurances

29. P4 will force a revision of business plans of
every sector of healthcare industry—
enormous economic opportunity
• Medicine--diagnostics, therapy, prevention, wellness
• Pharmaceuticals
• Biotechnology Healthcare
System
• Diagnostics and Devices
• IT for healthcare
New ideas generally need new
• Health insurance
organizational structures
• Nutrition
• Assessments of environmental toxicities/influences
• Academia and medical schools

30. ISB’s Strategic Partners for P4
Medicine
• Develop the tools and strategies for
systems biology and P4
– State of Luxembourg--$100 million over 5
years
• Bring P4 medicine to patients and
validate its power
– non-profit ISB-spinout P4 Medical Institute
(P4MI) in partnership with Ohio State Medical
School—two pilot projects—wellness and
heart failure

31. Systems Biology drives a cycle of innovation
Commercial
opportunities
Biology
Cross-Disciplinary Systems Biology seeks to
Culture address important and complex
Team Science problems in biology that have
previously been intractable.

32. ISB Companies
• Accelerator
o Commercializing cutting edge ideas in systems biology and related fields
o Established 2003
o 11 new companies founded, 7 still operating
o More than 750 business plans reviewed
o 100 visits from all over the world
o ISB receives founders equity / long-term endowment
• ISB Spin Offs
o Cytopeia - cell sorting – acquired - $1.1 million to ISB
o Macrogenics - antibody therapies
o Nanostring - digital mRNA counting
o Integrated Diagnostics - multiparameter blood protein
diagnostics
o Accelerator
o Future companies – wellness
Bottom line
o Raised $377 million in venture funding
o These companies have 328 employees

33. Sustainability: Education
All K-12 students should have
access to research-based
science education experiences.
– Skilled Workforce
– Educated Citizenry
– Future scientists and engineers

34. Center for Inquiry Science
• Center for Inquiry Science—embedded in ISB—6 full time
professional teachers—focus on K-12 science education
• Brings professional training to teachers for (inquiry-based)
science
• 2010 KCTS Golden Apple Award
• Unique partnerships with school district
• Representing 44% of student population in WA State
• Approximately 1,000 teachers trained every year; more
that 5,000 trained in last 5 years
• Remarkable success closing the achievement gap for
highest poverty schools.

35. SOME NUMBERS:
I am 2 meters tall
Cells are ~30 um (30 millionths of a meter)
I have ~10 trillion cells
10,000,000,000,000
Human genome sequence finished in 2003
Cost ~$2.7 Billion – now ~$5000
Each cell contains 23 pairs of chromosomes
That is ~3 billion (3,000,000,000 ) base pairs (AGCT)
Stretched end to end- ~ 3m of DNA/cell
DNA from all cells would stretch to the
sun and back ~70 times
~23,000 genes in humans (more proteins)
>100,000 protein interactions
~12,000 genes change their expression upon infection
with Vaccinia virus