Difference between revisions of "Team:William and Mary/Description"

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In natural systems, information is usually transmitted dynamically, that is, information is transmitted based upon how the system changes over time, rather than by the system’s value at any given point in time. One prominent example of dynamical information transmission is the p53 mediated response to DNA damage. In this system, the dynamics of p53 encode both the source and severity of the DNA damage (Figure 1) [1].  
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In natural systems, information is usually transmitted dynamically, that is, information is transmitted based upon how the system changes over time, rather than by the system’s value at any given point in time. One prominent example of dynamical information transmission is the p53 mediated response to DNA damage. In this system, the dynamics of p53 encode both the source and severity of the DNA damage (Figure 1).
 
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Figure 1: Schematic of an Incoherent Feed Forward Loop architecture. An activator (green) activates the production of a reporter/output (purple) as well as an inhibitor of the reporter (blue).
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Importantly, different sources of DNA damage lead to information being encoded in the dynamics of p53 in a qualitatively distinct manner. When the source of DNA damage is ultraviolet radiation, information is encoded in the form of a single pulse of variable amplitude and duration, whereas when the damage results from gamma radiation, information is encoded in a variable number of fixed height pulses. Since these two different encoding schemes lead to radically different pathways (cell cycle arrest and apoptosis respectively), any synthetic system that hopes to interact with this or any of the millions of other dynamical signaling pathways will need to be able to appropriately distinguish and process the different types of encoding schemes.
 
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Figure 2: Schematic of an Incoherent Feed Forward Loop architecture. An activator (green) activates the production of a reporter/output (purple) as well as an inhibitor of the reporter (blue).
 
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Based on abstract mathematical modeling, IFFLs are predicted to be temporal distinguishers, meaning their output is different depending on how the input was delivered. When subjected to a continuous input, the output is expected to be a pulse. When subjected to a pulsatile input, we expect to see a stepwise output. (cite plos)</div>
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This phenomenon of dynamic information encoding is not restricted to p53. In fact, it is wide spread throughout natural systems, with information being encoded in this manner in systems as varied as amoeba development, yeast stress response, immune function, and the maintenance of stem cells. This presents an obstacle for synthetic biologists hoping to study or interact with these systems, as there are currently no synthetic systems explicitly designed to distinguishing and processing information encoded in this dynamic manner. Further, if synthetic systems are to emulate the diversity and complexity of natural systems, they will need to be able to harness the power inherent in dynamic information processing. To address this problem, our project this year focused on the design and creation of a synthetic circuit capable of converting the dynamic information present in natural systems into a form usable by existing synthetic circuits. This circuit, which we term the decoder, would be of great use to field, enabling more effective integration of synthetic and natural systems. <a href = '' style = 'color:green;'>Click to read about our results</a>.
  
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The p53 tumor suppressor gene mentioned earlier is built on an IFFL motif, as are many other relevant systems, such as ERK in determining cell fates. Clearly, IFFLs play a unique and critical role in biology, so bringing their decoding abilities into SynBio could offer boundless research opportunities.</div>
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<div style = 'padding-left: 8%; padding-bottom: 10px;font-size: 25px' ><b>Our Project</b></div>
 
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Our team created an IFFL mathematical model tuned specifically to our system. Based on our modeling, we designed and constructed various IFFL circuits. We then investigated how these circuits responded to varying temporal inputs. Our results can be found here: link.</div>
 
 
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By researching the dynamics of genetic circuits, we are opening the doors to new possibilities in synthetic biology relating to dynamic signaling, thus broadening the ability of synthetic biologists to interact with natural systems. Through building and characterizing a diverse set of IFFL circuits, we have given every iGEM team access to the unique abilities of this genetic motif. We hope that teams will continue with our foray into the advancing field of dynamics within SynBio. </div>
 
  
 
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Revision as of 18:56, 17 October 2018

Page Title

Background

Motivation
A fundamental goal of synthetic biology the to be able to create synthetic systems capable of effectively interface with natural systems. From synthetic organs to the production of biomaterials, the applications of synthetic biology require that synthetic systems are capable interacting with and interpreting the signals used by natural systems. However, the field of synthetic biology currently lacks in the ability to interact with the rich dynamical encoding systems present in natural systems. This fundamentally limits our abilities to create interactive synthetic systems.
In natural systems, information is usually transmitted dynamically, that is, information is transmitted based upon how the system changes over time, rather than by the system’s value at any given point in time. One prominent example of dynamical information transmission is the p53 mediated response to DNA damage. In this system, the dynamics of p53 encode both the source and severity of the DNA damage (Figure 1).
Figure 1:
Importantly, different sources of DNA damage lead to information being encoded in the dynamics of p53 in a qualitatively distinct manner. When the source of DNA damage is ultraviolet radiation, information is encoded in the form of a single pulse of variable amplitude and duration, whereas when the damage results from gamma radiation, information is encoded in a variable number of fixed height pulses. Since these two different encoding schemes lead to radically different pathways (cell cycle arrest and apoptosis respectively), any synthetic system that hopes to interact with this or any of the millions of other dynamical signaling pathways will need to be able to appropriately distinguish and process the different types of encoding schemes.
This phenomenon of dynamic information encoding is not restricted to p53. In fact, it is wide spread throughout natural systems, with information being encoded in this manner in systems as varied as amoeba development, yeast stress response, immune function, and the maintenance of stem cells. This presents an obstacle for synthetic biologists hoping to study or interact with these systems, as there are currently no synthetic systems explicitly designed to distinguishing and processing information encoded in this dynamic manner. Further, if synthetic systems are to emulate the diversity and complexity of natural systems, they will need to be able to harness the power inherent in dynamic information processing. To address this problem, our project this year focused on the design and creation of a synthetic circuit capable of converting the dynamic information present in natural systems into a form usable by existing synthetic circuits. This circuit, which we term the decoder, would be of great use to field, enabling more effective integration of synthetic and natural systems. Click to read about our results.