Team:William and Mary/Description
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) [1].
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).
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).
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)
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.
Our Project
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.
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.