Team:UT-Tokyo/Sudoku abstract

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= '''Sudoku''' =
= '''Sudoku''' =
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        <ul id="inpagemenu">
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                <li><span>Introduction</span></li>
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                <li><a href="/Team:UT-Tokyo/Sudoku_construct" id="construct">System</a></li>
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                <li><a href="/Team:UT-Tokyo/Sudoku_modeling" id="modeling">Modeling</a></li>
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                <li><a href="/Team:UT-Tokyo/Sudoku_experiments" id="experiment">Experiments</a></li>
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                <li><a href="/Team:UT-Tokyo/Sudoku_perspective" id="perspective">Perspective</a></li>
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            <li><a href="/Team:UT-Tokyo/Sudoku_reference" id="reference">Reference</a></li>
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Abstract   
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== '''Introduction''' ==
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[https://2010.igem.org/Team:UT-Tokyo/Sudoku_construct  Construct]   
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[https://2010.igem.org/Team:UT-Tokyo/Sudoku_lab_note  Lab note]       
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[https://2010.igem.org/Team:UT-Tokyo/Sudoku_result  Result]
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== '''Abstract''' ==
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==='''Background'''===
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The ability to integrate and process information is indispensable for biological devices that operate autonomously in intricate environments, such as in "smart drugs", which sense and respond to the patient's health state appropriately.
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Therefore, the design and construction of such genetic circuits has long been pursued in the field of synthetic biology since its inauguration. Accomplishments include the toggle switch, logic gate, counter, and flip-flop switch.
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We're trying to make ''E.coli'' solve Sudoku puzzle. Human and Computers can solve Sudoku, of course. But ''E.coli'', which is lower animal, solves sudoku in our project. It is very very interesting!
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However, the function of most of these circuits is either limited to relatively simple form, such as Boolean logic element, or not robust enough to work correctly. A universal means of communication between individual elements is also generally lacking. As part of the solution, here we propose a new information processing unit which receives multiple inputs, memorizes the inputs stably, and makes a decision based on the combination of the inputs. In addition, we have devised a means of communication between individual bacterial-based elements. Importantly, this system allows destination-specific delivery of information even when the number of possible destinations is immensely large. As proof-on-principle of the above systems, we have created bacteria that solve "Sudoku", a world famous puzzle game.
==='''What is Sudoku?'''===
==='''What is Sudoku?'''===
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[[Image:What_Sudoku_99.png|200px|thumb|What's Sudoku?]]
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[[Image:9x9.png|200px|thumb|The example of Sudoku (9x9)]]
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Sudoku is a puzzle game with the objective of filling a 9x9 grid of cells with the numbers 1~9 without entering the same number in a column, row or “block (see figure).”
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Sudoku is a puzzle game with the objective of filling a 9x9 grid of cells with the numbers 1~9 without entering the same number in a column, row or “block (see figure).” A player is given a grid in which some of the cells are filled in from the beginning and must complete filling in the grid by entering the remaining numbers. The rules are simple, but some puzzles can get very difficult, and it attracts fans from all over the world. For simplicity, here we solve a 4x4 grid version. However, expanding on the same principles, our ''E. coli'' can theoretically solve larger grids, for example 9x9 grids.
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A player is given a grid in which some of the cells are filled in from the beginning and must complete filling in the grid by entering the remaining numbers.
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==='''Solving Sudoku with our ''E. coli'''''===
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[[Image:E.coli corresponding.png|200px|thumb|16 kinds of ''E. coli'' corresponding to each cell]]
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==='''Solution unique to the microbe: parallel computing'''===
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[[Image:Differentiation-model.png|200px|thumb|Every cells can "differentiate"]]
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[[Image:E.coli_info.png|200px|thumb|Each E.coli possesses two information]]
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[[Image:Parallel_computing.png|200px|thumb|Every cells "consider" independently]]
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When we solve Sudoku, either manually or by using a calculator, we usually enter random numbers in the grid one by one and look for the correct combination by trial-and-error. On the other hand, our E. coli are each capable of independently filling in the boxes simultaneously. In other words, our E. coli perform parallel computing.
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Now, we explain how to make ''E. coli'' solve Sudoku. First, we make 16 kinds of ''E. coli'' corresponding to each cell.
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==='''How to solve Sudoku?'''===
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Our E. coli are in one of two states, which we designate “differentiated” or “undifferentiated.” There are four differentiated states corresponding to the numbers from one to four.
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To solve Sudoku by human or the computer, we have to check the candidate of numbers which matches the rules for each 9x9 boxes. On the other hand, E. coli can fill in all boxes at a time by the system below.<br>
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-Judging all boxes simultaneously.<br>
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-Getting information about the location. (Which boxes they are in?)<br>
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-Outputting the correct number.<br>
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In other words, we propose the possibility of the new method of calculation, parallel computing, which has never been realized by traditional computers.
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Differentiated ''E. coli'' have the ability to inform other bacteria what number they are, so that relevant bacteria do not differentiate into that number. Some ''E. coli'' are differentiated from the beginning. These bacteria set in action a chain of transmission events that result in the differentiation of bacteria corresponding to all 16 cells.
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These events take place in a flask which contains a co-culture of the 16 types of bacteria. Each of these 16 types interacts with detection bacteria on a plate which in turn inform the viewer the number which the 16 cells have differentiated into with the use of fluorescent proteins.
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==='''Differentiation model in prokaryote'''===
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If you'd like to know how our ''E.coli'' solves SUDOKU particularly, please see the [https://2010.igem.org/Team:UT-Tokyo/Sudoku_construct  System] page.
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Instead of the traditional 9x9 grid of cells, we use E. coli possessing information of its location within the grid, in a liquid mixture.
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At the beginning, most of the bacteria are not designated a number while some of them are designated as an initial condition. Through undesignated bacteria receive information from their environment, they are designated a number, causing them to “differentiate” into a state in which they emit viruses possessing information of the bacterium’s location and number. These viruses in turn collectively compel other bacteria to be designated a particular number.
 
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In such a system, each bacterium must be able to identify relevant information, retain this information, and finally amass this information to “differentiate” into a particular number.
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To realize this, we use DNA recombination caused by proper virus.
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==='''Differentiation model in prokaryote'''===
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E. coli in each box rearrange DNA and determine their numbers by receiving information about the number from other E. coli in the same row, column, and block. In other words, they change their states irreversibly from “the multi-output state” to “the uni-output state.”
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We realize this by making a switch we named “4C3 leak switch,” using the leak of terminators. This switch turns on when three of four choices are transmitted, regardless of the order of transmission.
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==='''Information transmission by virus'''===
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To transmit information for proper E. coli, we use RNA phage named “signal virus.” Translation of the RNA transmitted from signal virus is controlled by antisense RNA characteristic to their location information.
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This destination-restricted information diffusion can be a powerful tool for building bio-computer, which use the creature as the unit of calculation.
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== Appeal point ==
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=== Parallel computing ===
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Our E.coli is superior to PC.
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=== Differentiation model ===
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This is a model of Eukarya differentiation model created by prokaryote.
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== Future vision ==
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Latest revision as of 03:57, 28 October 2010

UT-Tokyo

Sudoku

Introduction

Background

The ability to integrate and process information is indispensable for biological devices that operate autonomously in intricate environments, such as in "smart drugs", which sense and respond to the patient's health state appropriately. Therefore, the design and construction of such genetic circuits has long been pursued in the field of synthetic biology since its inauguration. Accomplishments include the toggle switch, logic gate, counter, and flip-flop switch.

However, the function of most of these circuits is either limited to relatively simple form, such as Boolean logic element, or not robust enough to work correctly. A universal means of communication between individual elements is also generally lacking. As part of the solution, here we propose a new information processing unit which receives multiple inputs, memorizes the inputs stably, and makes a decision based on the combination of the inputs. In addition, we have devised a means of communication between individual bacterial-based elements. Importantly, this system allows destination-specific delivery of information even when the number of possible destinations is immensely large. As proof-on-principle of the above systems, we have created bacteria that solve "Sudoku", a world famous puzzle game.

What is Sudoku?

The example of Sudoku (9x9)

Sudoku is a puzzle game with the objective of filling a 9x9 grid of cells with the numbers 1~9 without entering the same number in a column, row or “block (see figure).” A player is given a grid in which some of the cells are filled in from the beginning and must complete filling in the grid by entering the remaining numbers. The rules are simple, but some puzzles can get very difficult, and it attracts fans from all over the world. For simplicity, here we solve a 4x4 grid version. However, expanding on the same principles, our E. coli can theoretically solve larger grids, for example 9x9 grids.

Solving Sudoku with our E. coli

16 kinds of E. coli corresponding to each cell
Every cells can "differentiate"

Now, we explain how to make E. coli solve Sudoku. First, we make 16 kinds of E. coli corresponding to each cell.

Our E. coli are in one of two states, which we designate “differentiated” or “undifferentiated.” There are four differentiated states corresponding to the numbers from one to four.

Differentiated E. coli have the ability to inform other bacteria what number they are, so that relevant bacteria do not differentiate into that number. Some E. coli are differentiated from the beginning. These bacteria set in action a chain of transmission events that result in the differentiation of bacteria corresponding to all 16 cells. These events take place in a flask which contains a co-culture of the 16 types of bacteria. Each of these 16 types interacts with detection bacteria on a plate which in turn inform the viewer the number which the 16 cells have differentiated into with the use of fluorescent proteins.

If you'd like to know how our E.coli solves SUDOKU particularly, please see the System page.