Difference between revisions of "Featured Parts:Cell-Cell-Signaling"

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==Introduction==
 
==Introduction==
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Coordinating the behavior of cells within a population requires cell-cell signaling.  Information transfer between different groups of cells can also be enabled by cell-cell signaling.  The registry contains parts and devices to enable this inter-cell communication.
+
Coordinating the behavior of cells within a population requires [[Help:Signalling|cell-cell signalling]].  Information transfer between different groups of cells can also be enabled by [[Help:Signalling|cell-cell signalling]].  The registry contains [https://parts.igem.org/cgi/partsdb/pgroup.cgi?pgroup=Signalling parts and devices] to enable this intercellular communication.
  
 
==Cell-cell signaling technology==
 
==Cell-cell signaling technology==
−
Most of the existing methods to enable cell-cell signaling borrow technology from bacterial quorum sensing systems <cite>Bassler</cite>.  The best characterized of these is the LuxI/R system from ''V. fischeri'' <cite>Nealson</cite> and its homologs.  LuxI is a synthase that converts SAM into a small molecule called an acyl-homoserine lactone (AHL).  That molecule can diffuse across cell membranes and is stable in growth media at a range of pH.  LuxR is a constitutively expressed protein that can bind AHL.  When bound to AHL it can stimulate transcription from the right hand lux promoter.  In the natural system, this promoter controls transcription of the LuxI enzyme leading to a positive feedback loop that increases transcription from the right hand lux promoter.  As well as controlling the transcription of luxI, the promoter also controls transcription of luciferase.
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Most of the existing methods to enable cell-cell signaling borrow technology from bacterial quorum sensing systems <cite>Bassler</cite>.  The best characterized of these is the [[Lux|LuxI/R]] system from ''V. fischeri'' <cite>Nealson</cite>.  LuxI is a synthase that converts S-adenosylmethionine (SAM) into a small molecule called an [[AHL|acyl-homoserine lactone (AHL)]].  That molecule can diffuse across cell membranes and is stable in growth media over a range of pH values.  LuxR is a constitutively expressed protein that can bind AHL.  When bound to [[AHL]] it can stimulate transcription from the right hand lux promoter.  In the natural system, this promoter controls transcription of the LuxI enzyme leading to a positive feedback loop that increases transcription from the right hand lux promoter.  In addition controlling the transcription of luxI, the promoter also controls transcription of luciferase.
  
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A range of similar systems exist in other bacteria using homologous proteins that synthesize and respond to slightly modified versions of the ''V. fischeri'' AHL molecules.  Differing levels of cross-talk exist among these different systems <cite></cite>
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A range of similar systems exist in other bacteria using homologous proteins that synthesize and respond to slightly modified versions of the ''V. fischeri'' [[Acyl-HSLs|AHL]] molecules.  Differing levels of cross-talk exist among these different systems.
  
 
==Device classes==
 
==Device classes==
−
A minimal set of devices to enable cell-cell signaling is a sender device and a receiver signal.  These devices are sufficient to enable basic communication between cells in a population of bacteria.  These devices have been defined and some proofs of concept tested.  We expect that further classes of devices will be described in the future.   
+
A minimal set of devices to enable cell-cell signaling is a sender device and a receiver device.  These devices are sufficient to enable basic communication between cells in a population of bacteria.  These devices have been defined and some proofs of concept tested.  We expect that further classes of devices will be described in the future.   
  
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===Sender devices===
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===Sender devices https://static.igem.org/mediawiki/parts/6/6d/Sendericonvsmall.jpg===
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Currently, we define a sender device as a device that accepts an input of PoPS and outputs a rate of signaling molecule synthesis.
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Currently, we define a sender device as a device that accepts an input of [[Help:Glossary:P#PoPS (Polymerase Per Second)|PoPS]] and outputs a rate of signaling molecule synthesis.
  
 +
===Receiver devices https://static.igem.org/mediawiki/parts/5/5b/Receivericonvsmall.jpg===
 +
We define a receiver device as a set of genetic elements that responds to an extracellular input signal by changing the [[Help:Glossary:P#PoPS (Polymerase Per Second)|PoPS]] output from the device.  That input signal might be any biomolecule produced by other cells in the same environment.  While we can envisage a number of families of receiver devices we are currently developing a family based on the Lux system of ''V. fischeri''.  This device family is described below.
 +
<br style="clear:both" />
 +
====LuxR Receiver Family====
 +
[[Image:Luxrreceiverschematic.png|thumb|right|500px|LuxR receiver device mechanism]]
 +
A schematic of device operation is shown right.  The [[AHL]] molecule is recognized by a member of the LuxR protein family.  This AHL-LuxR complex can bind to an operator site upstream of a [http://rosalind.csail.mit.edu/r/parts/partsdb/view.cgi?part_id=192 Luxp<sub>R</sub>] family promoter and activate transcription.  The exact mechanism and stoichiometry of this activation have not been fully resolved. The degree of transcriptional activation can be set by varying the specific receiver protein, signaling molecule or promoters used.
  
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===Receiver devices===
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'''Device Input:''' [[Acyl-HSLs|Acyl homoserine lactone (AHL)]]<br/>
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We define a receiver device as a device that accepts an input of a signaling molecule and produces a PoPS output.
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'''Device Output:'''[[Help:Glossary:P#PoPS (Polymerase Per Second)|PoPS]]<br/>
 +
'''Relevant Device Characteristics'''<br/>
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*[[Featured Parts:Cell-Cell-Signaling/Transfer function|Transfer function]]
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*Variation in transfer function
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*[[Featured Parts:Cell-Cell-Signaling/Latency|Latency]]
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*[[Featured Parts:Cell-Cell-Signaling/Specificity|Specificity]]
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*[[Featured Parts:Cell-Cell-Signaling/Stability|Stability]]
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*[[Featured Parts:Cell-Cell-Signaling/Demand|Demand]]
 +
 
 +
 
 +
 
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[[Image:F2620Parts.png|thumb|left|200px|The base part structure of the receiver device. The specific example shown is F2620]]
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<br style="clear:both" />
  
 
==The parts==
 
==The parts==
 +
===Senders===
 +
*[https://parts.igem.org/wiki/index.php/Part:BBa_F1610 BBa_F1610]
 +
===Receivers===
 +
*[https://parts.igem.org/wiki/index.php/Part:BBa_F2620 BBa_F2620] <--includes characterization data
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*[https://parts.igem.org/wiki/index.php/Part:BBa_F2621 BBa_F2621]
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*[https://parts.igem.org/wiki/index.php/Part:BBa_F2622 BBa_F2622]
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*[https://parts.igem.org/wiki/index.php/Part:BBa_T9002 BBa_T9002]
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===Other relevant parts & devices===
 +
*[https://parts.igem.org/wiki/index.php/Part:BBa_I13015 BBa_I13015](currently listed as missing in the registry database, this is a sender device controlled by an inducible pBAD promoter.)
 +
*All the senders and receivers listed above use the 3OC<sub>6</sub>HSL signaling channel, however there are senders and receivers and the component parts specified or existing for each of the other well known signaling channels.
 +
 +
==References==
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*[[Lux]] - Registry's introduction to the Lux operon with links to outside sources
 +
<biblio>
 +
#Bassler pmid=16212498
 +
#Nealson pmid=396467
 +
</biblio>

Latest revision as of 23:51, 13 February 2007

Introduction

Coordinating the behavior of cells within a population requires cell-cell signalling. Information transfer between different groups of cells can also be enabled by cell-cell signalling. The registry contains parts and devices to enable this intercellular communication.

Cell-cell signaling technology

Most of the existing methods to enable cell-cell signaling borrow technology from bacterial quorum sensing systems Bassler. The best characterized of these is the LuxI/R system from V. fischeri Nealson. LuxI is a synthase that converts S-adenosylmethionine (SAM) into a small molecule called an acyl-homoserine lactone (AHL). That molecule can diffuse across cell membranes and is stable in growth media over a range of pH values. LuxR is a constitutively expressed protein that can bind AHL. When bound to AHL it can stimulate transcription from the right hand lux promoter. In the natural system, this promoter controls transcription of the LuxI enzyme leading to a positive feedback loop that increases transcription from the right hand lux promoter. In addition controlling the transcription of luxI, the promoter also controls transcription of luciferase.

A range of similar systems exist in other bacteria using homologous proteins that synthesize and respond to slightly modified versions of the V. fischeri AHL molecules. Differing levels of cross-talk exist among these different systems.

Device classes

A minimal set of devices to enable cell-cell signaling is a sender device and a receiver device. These devices are sufficient to enable basic communication between cells in a population of bacteria. These devices have been defined and some proofs of concept tested. We expect that further classes of devices will be described in the future.

Sender devices Sendericonvsmall.jpg

Currently, we define a sender device as a device that accepts an input of PoPS and outputs a rate of signaling molecule synthesis.

Receiver devices Receivericonvsmall.jpg

We define a receiver device as a set of genetic elements that responds to an extracellular input signal by changing the PoPS output from the device. That input signal might be any biomolecule produced by other cells in the same environment. While we can envisage a number of families of receiver devices we are currently developing a family based on the Lux system of V. fischeri. This device family is described below.

LuxR Receiver Family

LuxR receiver device mechanism

A schematic of device operation is shown right. The AHL molecule is recognized by a member of the LuxR protein family. This AHL-LuxR complex can bind to an operator site upstream of a [http://rosalind.csail.mit.edu/r/parts/partsdb/view.cgi?part_id=192 LuxpR] family promoter and activate transcription. The exact mechanism and stoichiometry of this activation have not been fully resolved. The degree of transcriptional activation can be set by varying the specific receiver protein, signaling molecule or promoters used.

Device Input: Acyl homoserine lactone (AHL)
Device Output:PoPS
Relevant Device Characteristics


The base part structure of the receiver device. The specific example shown is F2620


The parts

Senders

Receivers

Other relevant parts & devices

  • BBa_I13015(currently listed as missing in the registry database, this is a sender device controlled by an inducible pBAD promoter.)
  • All the senders and receivers listed above use the 3OC6HSL signaling channel, however there are senders and receivers and the component parts specified or existing for each of the other well known signaling channels.

References

  • Lux - Registry's introduction to the Lux operon with links to outside sources

<biblio>

  1. Bassler pmid=16212498
  2. Nealson pmid=396467

</biblio>