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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