Team:Paris Liliane Bettencourt/Project/Memo-cell

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<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell">
<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell">
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  <img src="https://static.igem.org/mediawiki/2010/e/e8/Memocell.png" width="75" height="75" title="Memo-Cell">
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  <img src="https://static.igem.org/mediawiki/2010/a/aa/Memo_cell-01.jpg" width="151" height="125" title="Memo-Cell">
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<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Synbioworld">
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  <font size=4>  Memo-Cell project</font>
  <font size=4>  Memo-Cell project</font>
<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/SIP">
<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/SIP">
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<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Population_counter">
<a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Population_counter">
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  <img src="https://static.igem.org/mediawiki/2010/3/30/Popcount.png" width="75" height="75" align=right title="Population Counter">
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   <li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell/Results" target="_self">Results</a></li>
   <li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell/Results" target="_self">Results</a></li>
   <li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Parts" target="_self">Parts</a></li>
   <li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Parts" target="_self">Parts</a></li>
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  <li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell/References" target="_self">References</a></li>
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<li><a href="https://2010.igem.org/Team:Paris_Liliane_Bettencourt/Project/Memo-cell/Materials" target="_self">Materials</a></li>
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Humans have invented many ways to count, from very simple manual counter to more
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complex logic gates implemented within electrical circuits.
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<br><br><br>
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==Introduction==
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<br><br>Counting is an essential process in our daily life, and implementing an automated counter
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<br>The Memo-cell project is a novel and original approach to allow for limitless counting of the signals a cell receives.
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into bacteria could have many applications, from medical to industrial.
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<br><br>Counting with bacteria is a concept that has already been tackled but which is still in its
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<br><br>Counting is an essential process in our daily life, and so humans have invented many ways to count, from very simple manual counters to more complex logic gates implemented within electrical circuits. Implementing a counter in bacteria is essential to a foundation on which more complex devices that produce different outputs according to a pre-set time sequence can be built.  
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infancy. Some counters have already been designed and implemented, but could only
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count up to three; though they could be extended. However, as these systems lie on
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the number of different transcription factors / recombination enzymes available AND
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characterized, extension to achieve counting more that 3 is pretty limited. Moreover, it is
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important to notice that for these designs, once an element as been used for counting, it
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can not be reused.
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<br><br>We propose here a completely novel and original approach to free from these constraints,
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<br><br>Counting with single-cells is a concept that has already been tackled but which is still in its infancy. Some counters have already been designed and implemented, but could only count up to three.  Extension of these existing systems to achieve counting to higher numbers has limited feasibility, as these systems are limited by the number of different transcription factors / recombination enzymes that are characterized and that do not interfere with each other or "cross-talk."  Moreover, it is important to notice that for these designs, once an element has been used for counting, it can not be reused.  
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allowing a limitless counting.
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<br><br>The framework for this approach is fairly simple. We will implement memory within the
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<br><br> In contrast, the approach we took here is free from these constraints, because we're using the same regulatory circuits cyclically. The framework for this approach is simple. We implement memory in the bacteria using a sequential integration of the same DNA pieces into the bacteria chromosome, controlled spatially and temporally. Memory will then be hardcoded in the genome by the number of DNA pieces integrated one after other in the genome.  
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bacteria using a sequential integration of DNA pieces into the bacteria chromosome,
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controlled in space an time.
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<br><br>Basically, the module we have developped is completely modular. To work, it just needs to
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<br><br>Our design hijacks the phage integration mechanism to allow the bacteria to integrate in its chromosome a specific piece of DNA at a specific location called attachment site, every time it detects a specific input signal. Then we regenerate this attachment site through a second recombination event, by again hijacking the transposon systems. The successive detection of signals will results in the successive integration of DNA pieces one after the other into the chromosome. The total number of DNA pieces integrated on the chromosome will then correspond to the number of times the signal has been detected. For instance, we could integrate the previously developed light sensing module and plug it to our memo-cell module. Hence, the memo-cell module would be triggered when there is light, and our bacteria will count the number of days.  
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be plug with an input module and an output module. Each time the input module will send
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a signal, our memory module will add one number to the count. When the memo-cell is
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used as a recorder, no output module needs to be connected. However, if a timer function
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is what you’re looking for, you can plug an output module which will be triggered when the
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counter will have counted up to the desired number.
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<br><br><u>Approach</u>
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<br><br>To achieve this goal, we had to extensively tinker with the following natural systems to engineer our three sub-modules, which we have done successfully in nearly 4 months of hard work:
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<br><br>Our plan is to create a mechanism that allows the bacteria to integrate in its chromosomee
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a specific piece of DNA at a specific location, everytime it senses the input signal.
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Moreover,
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<br><br>What we need:
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<br><br>Bacteria can manipulate DNA with ease, let’s use this property.
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e
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<br><br>Even if bacteria are «less» complex than us, they can be very useful as it has been proved
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during the last years since the beginning of synthetic biology.
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*  1. The recombination system of Phages Lambda and HK022;
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*  2. The recombination system of Transposon Tn916;
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*  3. The microcin C51 from a specific E.coli strain.
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With all the key components working, we have the full confidence of realizing our full system to count a fairly large number.
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<br><br><img src="https://static.igem.org/mediawiki/2010/0/02/Brickage-01.jpg" width=100%></html>

Latest revision as of 02:58, 28 October 2010


Memo-Cell project





Introduction


The Memo-cell project is a novel and original approach to allow for limitless counting of the signals a cell receives.

Counting is an essential process in our daily life, and so humans have invented many ways to count, from very simple manual counters to more complex logic gates implemented within electrical circuits. Implementing a counter in bacteria is essential to a foundation on which more complex devices that produce different outputs according to a pre-set time sequence can be built.

Counting with single-cells is a concept that has already been tackled but which is still in its infancy. Some counters have already been designed and implemented, but could only count up to three. Extension of these existing systems to achieve counting to higher numbers has limited feasibility, as these systems are limited by the number of different transcription factors / recombination enzymes that are characterized and that do not interfere with each other or "cross-talk." Moreover, it is important to notice that for these designs, once an element has been used for counting, it can not be reused.

In contrast, the approach we took here is free from these constraints, because we're using the same regulatory circuits cyclically. The framework for this approach is simple. We implement memory in the bacteria using a sequential integration of the same DNA pieces into the bacteria chromosome, controlled spatially and temporally. Memory will then be hardcoded in the genome by the number of DNA pieces integrated one after other in the genome.

Our design hijacks the phage integration mechanism to allow the bacteria to integrate in its chromosome a specific piece of DNA at a specific location called attachment site, every time it detects a specific input signal. Then we regenerate this attachment site through a second recombination event, by again hijacking the transposon systems. The successive detection of signals will results in the successive integration of DNA pieces one after the other into the chromosome. The total number of DNA pieces integrated on the chromosome will then correspond to the number of times the signal has been detected. For instance, we could integrate the previously developed light sensing module and plug it to our memo-cell module. Hence, the memo-cell module would be triggered when there is light, and our bacteria will count the number of days.

To achieve this goal, we had to extensively tinker with the following natural systems to engineer our three sub-modules, which we have done successfully in nearly 4 months of hard work:

  • 1. The recombination system of Phages Lambda and HK022;
  • 2. The recombination system of Transposon Tn916;
  • 3. The microcin C51 from a specific E.coli strain.

With all the key components working, we have the full confidence of realizing our full system to count a fairly large number.