welcome igem team 2007
Post on 15-Jan-2016
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Welcome iGEM team 2007 Research at the Interface
Engineering
Biology
Chemistry
Computer Science
PhysicsEconomics
Programming Cells
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
#include <iostream> main() { int input;cout << “Please Enter 0 or 1”;cin >> input;if (input = = 1)
cout << “Hello iGEM"; else
cout << “Goodbye”;
return 0; }
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Chemical A
Activator
Gene
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Chemical A
Activator
Gene
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Chemical AActivator
Gene
mRNA
Protein
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Repressor
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Chemical A
Repressor
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Chemical ARepressor
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Goal:Can we Program cells in a manner analogous to how we nowprogram computers?
Programming Cells
PromoterRegion
Repressor
Chemical A
mRNA
Protein
Cellular Pseudocode
{read in input; //light, chemical, etc
if (input is equal to “Chemical A”)“Turn on Gene 1”;
else“Gene 1 remains off”;
}
Programming Cells
But Really We would like to “write more complex cellular programs”
dozens of lines of code (or even 100s)
Multiple input typesMultiple output typesCrosstalkLoopsCounters
Perform a Variety of Activities
Engineering BiologyEngineering
-Framework for Design
We would like a toolbox of Modular Genetic Parts-Standardized Parts (BioBricks)-Swap components- Put together in new ways to perform new function -Portability - Transfer into new organisms or strains -Ability to program
Parts Devices Systems
Library ofPartshttp://parts.mit.edu
Build DevicesWith the Parts
Link Devices Together
Hierarchy:
http://parts.mit.edu
BioBrick Parts Assembly Strategy
The Cell is a Complex System
Schematic of an E. coli cell, by D. Goodsell, Scripps
Dynamic System
Although we do know the complete set of genes for many organisms
We don’t know exactly how everything works together (Goal of Systems Biology)
Synthetic BiologyResearch at the Interface
What can we do with reprogrammed cells:
1. Harness for production (metabolic engineering)-Introduce New Pathways
-Malarial Drug (artemisinin)
2. Coordinate Behavior of CellsTarget cells to tissues or other cell typesRespond to disease states or disease cells (biosensor, target cell death)2-D Patterns
3. Bacteria to Build or Fabricate Systems
Sensors
Sensors-respond to external commands
-Can be used to turn genes on and off-Control motility, etc
3. Environment Responsive Promoter
1. Cytoplasmic Regulatory Proteins
4. Regulatory RNAs
2. Two-Component Systems
Sensors
Cytoplasmic Regulatory Proteins- Inducers – Usually a small molecule – pass through cell membrane
binds to a cytoplasmic regulatory protein1. Turn on an activator2. Turns off a repressor
Graded population induction(All cells behave similar)
Intermediate Induction Difficult
Basal activity
Maximal Induced State
Dynamic Range of Induction
SensorsTwo Component Systems -Membrane Bound Sensor with Kinase Domain
-Responds to different stimuli (light, temp, chemicals)-Phosphorylates a Response Regulator (Triggers Transcription, binds promoter)
Sensor Domain
Kinase Domain P
NarX
tar
SensorsEnvironmental Response Promoters - pH, temp, Oxygen, UV light
-might not know the protein elements involved (but know result)
Sensor Domain
Kinase Domain P
NarX
tar
PromoterRegion
UV light DegradecI repressor
System used in “Tumor Killing Bacteria”-Anaerobic Inducible Promoter
SensorsRegulatory RNAs
RNA aptamers – Change Conformation when bound to small molecule, protein, or peptide
Potentially can be used to regulate any gene
Off conformation(ligand not bound)
On conformation(ligand bound)
On ConformationBinds to target transcriptAnd inhibits transcription(Antisense)
Schematic by C. Smolke
Genetic CircuitsGenetic Circuits
Enable Cells to- Process Input Signals- Make Logical Decisions- Cell-Cell Comunication
Switch-Used to turn on Gene Expression (once input is above a threshold)
Forms:Transcriptional Activators or RepressorsPre-transcription
Genetic CircuitsInverter – a switch that produces a reciprocal response (logic gate)
onrepressor
off
Toggle Switch – can exist in two states-where one or the other repressor is fully expressed-switch can be flipped between states
Genetic Circuits
GFP in a single cell over time (Elowitz and Leibler)
Dynamic Circuits- Oscillator – Cascade
- 3 Repressors
Genetic CircuitsCell – Cell Communication
Sender Cell Receiver Cell
acyl-homoserine lactone (AHL)
Figure from Basu … Weiss
Chemical Signal
ActuatorsActuators-To control the outputMechanical Device for Moving a SystemInvasion of Malignant Cells (hypoxic environment triggers invasion of cells)
Y. pseudotuberculosisinvasin
In Conclusion
We now have the tools to build new and exciting devices within biological cells
Where we can construct new parts, new devices, and new systems
We can build on previous work in Synthetic Biology
Develop novel uses for this technology (Medical applications)
Share with others through iGEM
Thanks!
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