Institute for Systems Biology

John Aitchison, Ph.D.

Professor

VP, Director for Integrative Biology

Three Pillars of ISB

Systems Biology

Collaborations

Partnerships

Commercial Spinouts

Stewardship

Education

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

Biology is a systems problem

• A system is any collection of interacting parts with

emergent behavior.

• Emergence is when the whole is greater than the sum of

the parts.

• Neutrophil – chasing down

bacteria to eat it

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.

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.

Biological Systems Are Self Organizing

Cells: dynamic networks of interacting components, with

millions of local interactions (systems)

DNA RNA Protein

Traditional approaches study a single

gene/RNA/protein at a time

But there are tens of thousands of genes/RNA/proteins!

Single gene

Time

DNA RNA Protein

A holistic view

Systems Biology

Driven by

computation

and technology

Systems Biology drives a cycle of innovation

Biology

Biological

Information

And Insight

Cross-Disciplinary

Culture

Team Science

Systems Biology seeks to

address important and complex

problems in biology that have

previously been intractable.

Systems Biology drives a cycle of innovation

Biology

Cross-Disciplinary

Culture

Team Science

Three Major Research Thrusts at ISB

Health Care

(P4 Medicine)

Sustainability

(BioEnergy)

Medical Research

(Global Health)

Solving Complex Problems Requires a Systems Approach

ISB is attacking these problems through partnerships.

Drive systems biology and apply in these major areas

Three Major Research Thrusts at ISB

Health Care

(P4 Medicine)

Sustainability

(BioEnergy)

Medical Research

(Global Health)

The fundamental challenge: How can we understand the emergent macroscopic properties of the

system from its parts and their interactions?

Analogy: circuit diagram

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’?

Stimulus

(fatty acids)

~40% of the genes change in

expression

PR

OG

RA

M o

f re

sponse

Systems biology to understand complex responses

- of cells - and of pathogens and hosts

(

Pathogen

~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)

PR

OG

RA

M o

f re

sponse

Systems biology to understand complex responses

- of cells - and of pathogens and hosts

Application of systems biology to vaccine

development

To identify predictors of vaccine

immunogenicity (signatures)

To understand the molecular

networks leading to a protective

response

To re-engineer the response with

adjuvants

Edward Jenner

1796

ISB-SBRI Partnership

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

Solving Complex Problems Requires a Systems Approach

Health Care

(P4 Medicine)

Sustainability

(BioEnergy)

Medical Research

(Global Health)

Solving Complex Problems Requires a Systems Approach

Health Care

(P4 Medicine)

Sustainability

(BioEnergy)

Medical Research

(Global Health)

Dynamics of a Brain Network in Prion

Neurodegenerative Disease

Prion accumulation network

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

Predictive, Personalized, Preventive

and Participatory (P4) Medicine

26

Genome sequence; multiparameter measurements; computation

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

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

• Medicine--diagnostics, therapy, prevention, wellness

• Pharmaceuticals

• Biotechnology

• Diagnostics and Devices

• IT for healthcare

• Health insurance

• Nutrition

• Assessments of environmental toxicities/influences

• Academia and medical schools

P4 will force a revision of business plans of

every sector of healthcare industry—

enormous economic opportunity

Healthcare

System

New ideas generally need new

organizational structures

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

Systems Biology drives a cycle of innovation

Biology

Commercial

opportunities

Cross-Disciplinary

Culture

Team Science

Systems Biology seeks to

address important and complex

problems in biology that have

previously been intractable.

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

Sustainability: Education

All K-12 students should have

access to research-based

science education experiences.

– Skilled Workforce

– Educated Citizenry

– Future scientists and engineers

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.

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