title

A SYSTEMS ENGINEERS INTRO TO SYSTEMS BIOLOGY A SYSTEMS ENGINEERS INTRO TO SYSTEMS BIOLOGY

The Institute for Systems Biology, Seattle

http://www.systemsbiology.org

systems biology simultaneously studies the complex interaction of many levels of biological information to understand how they work together. “

“Systems Biology is:

a powerful approach to studying complex biological systems

made possible through technological breakthroughs such as the human genome project.

Unlike traditional biology that examines single genes or proteins in isolation,

SYSTEMS BIOLOGY – SOME CONCLUSIONSSYSTEMS BIOLOGY – SOME CONCLUSIONS

“Systems biology offers exiting improvements in our understanding of complex, biological systems“

Most biological entities are systems

A “systems approach” should definitely help

No clear definition of system

Many different approaches

But:

*Chem & Eng News, May 19, 2003, Volume 81, Number 20 pp. 45-55

“...although there's not yet consensus on what systems biology actually is*...”

MY DEFINITION OF SYSTEMS BIOLOGY MY DEFINITION OF SYSTEMS BIOLOGY

“The application of Systems Engineering Principles/Practices,

Systems Biology is:

To the understanding* of Biological Systems, especially the human biological system”

created for the development and understanding of ‘inanimate systems’,

*through bio-medical research

PRESENTATION OUTLINEPRESENTATION OUTLINE

Systems Engineering Overview

Applications to Systems Biology

“Derive” Human Body Plan

From fundamental biological requirements

Sys engng overview

SYS ENGNG – APPROACH – FORWARDSYS ENGNG – APPROACH – FORWARD

Need Reqmnts+

Test Plan

Concept* Design* TestFab

PrototypeText

Fab and Assembly Drawings

Create Test Plan

Analyses/simulation

?

Test Results

*Additional, sub requirements at these stages

+ Requirements provide “why?”

DocumentsCreated

Hierachical Diags

Block Diags

Data Flow Diags Parts lists

SYS ENGNG – APPROACH - REVERSESYS ENGNG – APPROACH - REVERSE

Create Test Plan

Test Plan

TestDisassemble

DocumentsCreated

Test Results

Design [1]

HAVE ITEM TO STUDYHAVE ITEM TO STUDY

[1] How did designer(s) proceed ?

Reqmnts [2] Concept

[2] Requirements explain why

Fab and Assembly Drawings

Parts lists

Hierachical Diags Block Diags Data Flow Diags Analyses/simulation

SYS ENGNG: TOP DOWN – BOTTOM UPSYS ENGNG: TOP DOWN – BOTTOM UP

Forward Systems Engineering – Top Down

Reverse Systems Engineering – Bottom Up

Systems Biology needs both

App Sys engng to sys bio

SYS ENGNG -> SYS BIO APPROACH - REVERSESYS ENGNG -> SYS BIO APPROACH - REVERSE

Create Test Plan

Test Plan

TestDisassemble

DocumentsCreated

Test Results

Design??

HAVE BIOLOGICAL ENTITY TO STUDYHAVE BIOLOGICAL ENTITY TO STUDY

Dissection

Trial and Error

Hierachical Diags Block Diags Data Flow Diags Analyses/simulations

Reqmnts [2] Concept

[2] Requirements give clues about why

How many genes are there and why?

What do all the proteins do and why?

Fab and Assembly Drawings

Parts lists

Anatomical drawings

bio-informatics*

*Science Magazine: 6 February 2004

TYPICAL BIOLOGICAL SYSTEM CONFIGURATION TYPICAL BIOLOGICAL SYSTEM CONFIGURATION HIERARCHICAL REPRESENTATIONHIERARCHICAL REPRESENTATION

System

Assemblies

Sub Systems

Subassemblies

Components

Biological Entity

Systems **

Organs

Tissues

Cells

** Conflict between established nomenclature and Systems Engineering Practice

. . . . . Molecules

Inanimate System Biological System

BIOLOGICAL BLOCK DIAGRAMSBIOLOGICAL BLOCK DIAGRAMS

RightAtrium

TricuspidValve

PulmonaryValve

Lung Lung

LeftVentrical

M itralValve

LeftAtrium

RightVentrical

Pulmveins

VenaCava

PulmArtery

AorticValve

To BodyFrom Body

contraction

contraction

SYS ENGNG -> SYS BIO APPROACH – FORWARDSYS ENGNG -> SYS BIO APPROACH – FORWARD

Need Reqmnts Concept Design TestFab

What requirements satisfy need?

What concept/ design meets requirements?

How is/was this “built”?

This approach can lead to interesting insights

Gain insights into origins of Human Behavior

Show that Human Body Plan is quite logical

Begin with need to survive

Concept/Design

SYS ENGNG -> SYS BIO: REQUIREMENTS ANALYSISSYS ENGNG -> SYS BIO: REQUIREMENTS ANALYSIS

Required Activity

Individual

O2 In CO2 Out Yes

Food In Waste Out

Yes

Proper Environment

Yes

Species

No

No

No

Reproduction No Yes

Territory Yes Yes

Survival: The most basic requirementSurvival: The most basic requirement

SUB REQUIREMENT RELATED TO REPRODUCTION SUB REQUIREMENT RELATED TO REPRODUCTION AND IMPLICATIONS FOR HUMAN BEHAVIORAND IMPLICATIONS FOR HUMAN BEHAVIOR

Birth rate, B >= Death Rate, D

B = D

B > D

Optimum, but too much variability in D

Only Practical Design

B > D leads to Exponential Growth

Since territory is finite

But, Sub Optimal

Growth leads to conflict

One of the origins of war

REPRODUCTION: CONCEPTULIZATIONREPRODUCTION: CONCEPTULIZATION

One possibility

How might reproduction be accomplished?

divide

That won’t work –

Thus, Reproduction must begin with single cell

Only animal that can divide: a single cell animal

Just get an aged copy Want to start young

REPRODUCTION: CONCEPT-DESIGNREPRODUCTION: CONCEPT-DESIGN

Actually need two cells

Design “Improvement” requires change

Single cell division just yields same animal

Evolution “designed” remarkable Reproductive System

Fused cell divides successively to create final biological system

“Fabricated” by meiosis

Two sex cells: Male and Female

Two cells fuse to create new, unique individual

BASIC BODY PLAN – INTERNAL SYSTEMSBASIC BODY PLAN – INTERNAL SYSTEMS

Respiratory

Reproductive

Digestive upper Circulatory

Spine

Digestive lower

Uro-gen Tract

O2 CO2 Food

Skincells

O2 In CO2 Out

Food In

Waste Out

Torso

Arrangement determined by requirements

BODY CONTROL SYSTEMBODY CONTROL SYSTEMBody Control System

Nervous SystemChemical Messenger System

Endocrine

paracrine

autocrine Central Peripheral

Brain Spinal Cord

Motor Neurons

Sensory Neurons

Brain neurotransmitters very similar to endocrine hormones

Slow, but flexible Fast Structured

Control via specialized molecules that act on receptors

Control via electrical impulses carried by specialized cells - neurons

Implement complex functions: emotions, cognition

Implement rapid sensory response and muscle control

BASIC BODY PLAN – HEADBASIC BODY PLAN – HEADIndividual survival requires environmental sensors

BRAIN

EYE EYE

EA

R

EA

R

M O UT H

NO

SE

FOODWAT ER

O2

C O2

Remainder of Body

Remote: Visual – Eyes, Audible - EarsClose-up: Smell - nose, taste - mouth

BASIC BODY PLAN – LOCOMOTION SYSTEMBASIC BODY PLAN – LOCOMOTION SYSTEM

Respiratory

Reproductive

Digestive upper Circulatory

Spine

Digestive lower

Uro-gen Tract

Arm - upper

Arm - Lower Hand

ArmHand

Leg - upper

Leg - Lower Foot

Foot Leg

Food In

Ability to get to food

BASIC BODY PLAN - COMPLETEBASIC BODY PLAN - COMPLETE

Respiratory

Reproductive

Digestive upper Circulatory

Spine

Digestive lower

Uro-gen Tract

Arm - upper

Arm - Lower Hand

ArmHand

Leg - upper

Leg - Lower Foot

FootLeg

BRAIN

EYE EYE

EA

R

EA

R

M O UT H

NO

SE

FOODWAT ER

O2

C O2

Neck

SOME WAYS SYS ENG CAN ASSIST SYS BIOSOME WAYS SYS ENG CAN ASSIST SYS BIO

Systems Engineering practices can assist Information organization, particulary bio-informatics

Systems Engineering Oriented Requirements Analysis can assist is in determing “why”

Systems Engineering Approaches can assist Bio-medical Research approaches

Biological Systems Engineer is logical counterpart to Systems Engineer

The end

SYSTEMS BIOLOGY QUO VADIS?SYSTEMS BIOLOGY QUO VADIS?

Financial Times May 29, 2005