CHE.496/2008/Responses/a11

Genetic circuit engineering (part 2)

• Discussion leader: Dan Tarjan (Discussion guide)

George McArthur's Response

• Environmentally controlled invasion of cancer cells by engineered bacteria
  • This paper describes the design of a very cool synthetic biological system that involves an engineered genetic circuit in bacteria. Essentially, the bacteria are equipped with sensing, processing and actuating abilities. This is the end goal of a genetic circuit engineering project - to have the cell behave like a programmed, yet biological, robot. In this case, the bacteria can sense cancer cells via heterologous environmental signals and, in response, invade and destroy these cells using invasin, a cytotoxic agent. The idea of programming a cell for a specific function is extremely exciting. Several project ideas should be generated with this in mind.
• Environmental signal integration by a modular AND gate
  • This paper is an extension of the previous paper and describes in detail the way in which their engineered bacteria integrate the heterologous environmental signals. The authors describe the moldular AND gate that is used to process the input signals and actuate the response, mammalian cell invasion/destruction. The AND gate uses "information from two promoters as input and activates a promoter output only when BOTH input promoters are transcriptionally active." This is a wonderfully detailed example of genetic circuit design and construction, and could serve as a guide to working through a new system design. In addition, the AND gate is modular so that the inputs and outputs can be changed by interchanging promoters and RBSs. Therefore, it could be used in a variety of engineering applications.
• GMcArthurIV 15:55, 26 February 2008 (EST)

Kevin Hershey's Response

• Environmentally controlled invasion of cancer cells by engineered bacteria
  • The article by Anderson et al describes a modification made to bacteria which allows it to swarm cancer cells and attack it. A modification was also made so that the blood cells don’t attack the E. coli. This can be applied to synthetic biology in several ways. First, standardizing the parts allows it to be used by other systems. For example, the Berkley team designed BactoBlood. This used the modified sensor in the E. coli to prevent human blood from attacking it. Also, with the principles of synthetic biology, modeling the E. coli is very important. In such a system as this, there must be extensive testing before it can be used in humans, whom the treatment is created for. The modeling can then be presented to the FDA to allow for clinical trials.
• Environmental signal integration by a modular AND gate
  • This article by Anderson describes an AND gate that reaches near-digital output. This can be very advantageous for the VGEM team, as this allows for another part in the ‘biological toolbox.’ Also, the modeling done by Anderson et al can be applied to a potential VGEM project. Their method of using fluorescence to model their output based on different inputs is a very common method. It is likely that a VGEM project will need to use their experimental design.
• KPHershey 16:17, 26 February 2008 (EST)

Patrick Gildea's Response

• Environmentally controlled invasion of cancer cells by engineered bacteria
• Environmental signal integration by a modular AND gate
• Patrick Gildea 17:47, 26 February 2008 (EST):