Systems biology is an approach that studies biological systems as a whole by considering the interactions between their parts. It uses techniques like genomics to understand complex systems like the human body. The document discusses how systems engineering principles can be applied to systems biology to better understand biological systems in a structured, top-down way by starting with requirements and working through concepts, designs, and testing, similar to how engineered systems are developed and analyzed. The human body plan in particular can be understood as logically derived from basic biological requirements for survival.
2. 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,
3. SYSTEMS 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*...”
4. 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
5. PRESENTATION OUTLINE Systems Engineering Overview Applications to Systems Biology “ Derive” Human Body Plan From fundamental biological requirements
7. SYS ENGNG – APPROACH – FORWARD Need Reqmnts + Test Plan Concept* Design* Test Fab Prototype Text 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
8. SYS ENGNG – APPROACH - REVERSE Create Test Plan Test Plan Test Disassemble DocumentsCreated Test Results Design [1] HAVE 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
9. SYS ENGNG: TOP DOWN – BOTTOM UP Forward Systems Engineering – Top Down Reverse Systems Engineering – Bottom Up Systems Biology needs both
10. App Sys engng to sys bio SYSTEMS ENGINEERING SYSTEMS BIOLOGY APPLYING PRINCIPALS/PRACTICES
11. SYS ENGNG -> SYS BIO APPROACH - REVERSE Create Test Plan Test Plan Test Disassemble DocumentsCreated Test Results Design?? HAVE 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
12. TYPICAL BIOLOGICAL SYSTEM CONFIGURATION HIERARCHICAL 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
14. SYS ENGNG -> SYS BIO APPROACH – FORWARD Need Reqmnts Concept Design Test Fab 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
15. SYS ENGNG -> SYS BIO: REQUIREMENTS ANALYSIS Required Activity Individual O 2 In CO 2 Out Yes Food In Waste Out Yes Proper Environment Yes Species No No No Reproduction No Yes Territory Yes Yes Survival: The most basic requirement
16. SUB REQUIREMENT RELATED TO REPRODUCTION AND 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
17. REPRODUCTION: 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
18. REPRODUCTION: 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
19. BASIC BODY PLAN – INTERNAL SYSTEMS Respiratory Reproductive Digestive upper Circulatory Spine Digestive lower Uro-gen Tract O 2 CO 2 Food Skin cells O 2 In CO 2 Out Food In Waste Out Torso Arrangement determined by requirements
20. BODY CONTROL SYSTEM Body Control System Nervous System Chemical 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
21. BASIC BODY PLAN – HEAD Individual survival requires environmental sensors Remainder of Body Remote: Visual – Eyes, Audible - Ears Close-up: Smell - nose, taste - mouth
22. BASIC BODY PLAN – LOCOMOTION SYSTEM Respiratory Reproductive Digestive upper Circulatory Spine Digestive lower Uro-gen Tract Arm - upper Arm - Lower Hand Arm Hand Leg - upper Leg - Lower Foot Foot Leg Food In Ability to get to food
23. BASIC BODY PLAN - COMPLETE Respiratory Reproductive Digestive upper Circulatory Spine Digestive lower Uro-gen Tract Arm - upper Arm - Lower Hand Arm Hand Leg - upper Leg - Lower Foot Foot Leg Neck
24. SOME 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
25. The end THE APPLICATION SYSTEMS ENGINEERING SYSTEMS BIOLOGY OF TO THE END
My carreer was spent working on “inanimate” sys, but always had interest in biology – esp bio-med research
On a trip to Wa a couple years ago, discovered this organization Sys bio naturally caught my interets Went to web site to learn more Being retired, had the time Found this definiton Found site very interesitng, but wasn’t clear exactly how sys bio worked Visited other sites, began for form opinion that sys engn could assit sys bio
Need is rearely well defined – must gen a list of requirements While requirements are generated, create test plan – all requirements must be testable and have a specific test After requirements, determine if there is a concept that will satisfy requirements. During cocept definition, gen many docs hierarchical diags identify elements block diagrams show hoe elements interconnect data flow diags show how info moves thru system and how control functions analyses and simulatio investigate dynamical aspects of system Assuming a reasonable concept, proceed to a design – gen fab/assy/parts lists After design complete, fab prototype Then proceed to test
Can work the process in reverse – beginning with completed system for which one wants to know how built etc Begin by conducting tests and dissasembling – gen drawings Try to understand what designer had in mind Try to determine what the requirements were that drove the concept/design
Much bio research is reverse engineering Change dissassembly to dissection Change fab/assy dwngs to anatomical dwngs Modern research adided by wide and growing variety test equipment/proceedures Design approach is “sticky wicket” , some believe supernatural being is designer, I beleive trial and error
Relation between system hierarchy and bio sys hierarchy
Diagrams anatomically oriented are necessary, but block diagrams assist in showing how bio sys function
Can use forward version of sys engng to gain unique insights
To illustrate some of the principles, will show how can use fwd engng in bio sys to deduce some basic aspects of human behaviour and the human body plan. Simplistic, but I think it will be interesting and perhaps informative – no new data, but a different way of viewing
Not objective to engage in controvesy – just want to show how req analysis can lead to interesting areas
“cartoon” block diagram showing placement of all but locomotion system We know from direct obs that most suys are contained in torso – see how requirements shows how they are arranged and why
BCS made of two sys, chem messenger communicates via special molecules – hormones that operate on receptors Nervous sys communicates via electrical impulses sent over special cells – neaurons Diagram created as shown since there are similarites between chem msngr and brain: neuro transmitters very sim to hormones
Must place environmental sensors in juxtapostion to brain since are high bandwidth 2 eyes and ears – 1 not enough, 3 too many
Need locomotion system to satisfy requirement for food in Two arms – 1 not enough, 3 too many
Human body plan is not accidental – but quite logocal. There are some sub optimum aspects, but these are reasonable compromises. If we ever meet extra terrestrial intelligent beings, they will look basically like us
How I got interested Brief results of inquiries -> sys engng should be able to help Brief over view sys engng Examples
$ billions are being spent to eliminate heart disease, cure cancer, etc. Unless these are fools errands, the end reult is elemination of the causes of death. Kurz and grossman beleive that at current pace of bio-med research, this is going to happen sooner than we beleive – so need to live long enough. On the other hand, there are those who worry about this