Breaking the Symmetry SEU_O Idea Outreach SEU_O System Design - PowerPoint PPT Presentation

Breaking the Symmetry SEU_O

Idea Outreach SEU_O System Design Experiments Scheme-Modeling

Centrosymmetric Isotropy Sy Symme mmetry ry Circularsymmetry Part 1 Idea homogeneity

To Break Symmetry ：

Breaking the Symmetry Differentiation

Communication Input Differentiation Output

System Design Part 2&3 && System Simulation

System Design Light Input

Light Sensor Light Sensor Input Light Receiver Light Differentiation Communication Downstream Gene Light Promoter Output

Light Toggle Sensor Switch Toggle Switch Input Input Signal Downstream Gene Differentiation Communication Status 1 Status 2 Output

Light Toggle AHL Sensor Switch Signal AHL Signal Input Differentiation AHL Receptor Communication Output AHL Generator Downstream Gene

Toggle Division Light AHL Switch Inhibitor Sensor Signal Division Inhibitor Input Differentiation Inhibitor Communication Output

Division Light Toggle AHL Inhibitor Sensor Switch Signal Light

Light Induced System

System Simulation %Light Induced Micro Model

Cellular Applications • Mathematics • Physics • Complexity Science • Theoretical Biology • Microstructure Modeling

Light Induced Micro Model --Control Group Three Basic Functions % Cell Division % Cell Movement % Molecule Diffusion

Light Induced Micro Model --Control Group Result

Experiment Group

Light Induced Micro Model --Experiment Group % Light as Input Input Differentiation Communication Output

Light Induced Micro Model --Experiment Group % Differentiation: From Green to Red Input Differentiation Communication Output

Light Induced Micro Model --Experiment Group % Red cell can release AHL Input -Improved AHL Diffusion Differentiation Communication  u: AHL density;  D: diffusion constant;  q: AHL releasing rate of a single triggered cell;  γ describes the decomposition process of AHL; Output  m: total number of cells.

Light Induced Micro Model --Experiment Group % Red cell can release AHL Input % Cell Division Inhibition -AHL trigger the division inhibitor Differentiation -Decrease cell division rate Communication Output

Light Induced Micro Model --Experiment Group Control Group Experiment Group Input Differentiation Communication Output

Light Induced Macro Model (More details @ our website) Experiment Group Control Group

System Design Input

Auto Differentiation System

Auto Differentiation System Input None Differentiation Communication Random Differentiation Output

Auto Differentiation System Input Differentiation Communication Output

Auto Differentiation System Chemotactic Migration Input Differentiation Communication Output

Auto Differentiation System Input Differentiation Communication Output

System Simulation %Auto-Differentiation Model

Auto-Differentiation Model % NO INPUT Input Differentiation Communication Output

Auto-Differentiation Model % New Cell Differentiate Randomly Input  P (New Cell is Red) P    P d) P Differentiation red       P (New Cell is Green) P Communication red   P n) 1 P red Output  P red is a constant, describing red cell rate.

Auto-Differentiation Model Red Cells: Input Move towards AHL Differentiation Release AHL Communication Cluster Output

Auto-Differentiation Model Input Move towards AHL Differentiation Release AHL Return to Light Communication Cluster Induced Model Output

Auto-Differentiation Model Experiment Group Input Control Group Differentiation Communication Output

Part 4 Experiment Design

Light Sensor Light Sensor • Red Light Toggle Switch AHL Signal • Blue Light Division Inhibitor

Light Sensor - Red Light Sensor Toggle Switch AHL Signal Division Inhibitor

Light Sensor - Red Light Sensor • Parts Toggle Switch • BBa_M30109 • BBa_S05053 (cph8) AHL • BBa_S05054 Signal (Ompc+RFP) Division Inhibitor

Light Sensor - Blue Light Sensor Toggle Switch AHL Signal Light Division Inhibitor

Toggle Switch Light Sensor Input Output UV Light Toggle Status 1 Status 2 Switch cI Promoter lac promoter AHL Signal lacI cI Division Inhibitor

Toggle Switch Light Sensor • Parts Toggle Switch • BBa_S05055(Lac promoter+cI) AHL Signal Division Inhibitor

AHL Signal Light Sensor LuxI LuxI Toggle Switch SAM AHL AHL AHL AHL AHL Signal Division LuxR Inhibitor Lux pR

Division Inhibitor Light Sensor FtsZ DNA ( From Genome) Toggle A Fragment Switch FtsZ mRNA AHL FtsZ protein Signal Expression Vector Cell Division Division Inhibitor Antisense FtsZ mRNA Fragment

Division Inhibitor Light Sensor • Parts • BBa_K897720(asFtsZ+ Paired termini) Toggle • BBa_K897624(asFtsZ+terminator) Switch • BBa_K897318(Paired termini) AHL Signal Division Inhibitor

Division Inhibitor Light Sensor • Results IPTG 0mM/L 0.5mM/L 1mM /L 2mM /L Toggle Switch Experiment group AHL Signal Control Division group Inhibitor

Part 5 Outreach

Overall Prospects ------more than creating a star Break the symmetry More accurate microarray Differentiation

Complex Microstructure Construction More Direct Bio-sensor Evolution Research

A Specific Example • Bio-Computer: networks that Rational execute input- interconnection of triggered genetic synthetic switches instructions Bio-logical Gates ------ Basic Units of Bio-computer Feasibility: Turing Machine; Advantages: Simple&&direct; Realization: Boolean algebra&&Threshold;

Bio-logical Gates(1) • 1 . A 2-Input NAND Gate Light Input Location: 35, 45. Cellular Density Output Location: 40. A 0 1 1 B 0 0 1 L 1 1 0

Bio-logical Gates(2) • 2. A 2-Input NOR Gate Light Input Location: 38, 42. Cellular Density Output Location: 40. A 0 0 1 B 0 1 1 L 1 0 0

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C)

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C)

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C)

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C)

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C)

Model Extension • Model for a Combinational Logical Gate • L=not((A*B)+C) A B C L 0 0 0 1 0 0 1 0 0 1 0 0 1 0 1 0 1 1 0 0 1 1 1 0

Part Application • A New Standard for Biosafety: Light-Controlled Colony Growth • A newly-built protection for antisense RNA sequences (paired termini structure)

Human Practice • Main Theme: Biosafety • 1. Domestic Survey • 2. Biosafety Training • 3. Innovation: a safer general transgenic vector

Scheme • Attach another division repressing part to the former light sensor

Others • Video • A short flash video named Synthetic Biology--- yesterday, today and tomorrow .

Others • Domestic Competition Organization • Lectures

Acknowledgements • We would like to convey our sincere thanks to many people , organizations and all our team members.

reference • [1] Oleg A. Igoshin et al. Breaking symmetry in myxobacteria, Curr Biol. 2004 Jun 22;14(12):R459-62. • [2] Alvin Tamsir et al. Robust multicellular computing using genetically encoded NOR gates and chemical ‘wires’, Nature 469, 212– 215 • [3] Simon Ausländer et al. Programmable single-cell mammalian biocomputers, Nature (2012) doi:10.1038 • [4]Anselm Levskaya et al. Synthetic biology: Engineering Escherichia coli to see light. Nature,November 24,2005.438:441-442 • [5]Jeffrey J.Tabor et al. A Synthetic Genetic EdgeDetection Program. Cell,June 26,137: 1272-1281 • [6] Hideki Kobayashi et al. Programmable cells: Interfacing natural and engineered gene networks. PNAS, April 26, 2004 • [7] http://partsregistry.org/Featured_Parts:Cell-Cell-Signaling • [8] http://partsregistry.org/wiki/index.php/Part:BBa_F2620