CHE.496/2008/Responses/a8

Engineering biology

• Discussion leader: Brandon Freshcorn (Discussion guide)

Kevin Hershey's Response

• A partnership between biology and engineering
  • The commentary by Roger Brent discusses the advantages of synthetic biologists with systems biologists. This is a logical progression for synthetic biologists, as synthetic biology is based on the individual parts. Just as synthetic biology combines different disciplines to be successful, so must it be a discipline in the larger sense of biological understanding. With the fusion of these two methodologies, computer scientists, biologists, electrical engineers, mathematicians, etc. can work towards a complete understanding of genetically modified bacteria. This combination of efforts will contribute to a better understanding of systems, and better predictive methods.

• Fast, cheap and somewhat in control
  • Another commentary, Arkin and Fletcher discuss the different problems and advantages to engineering systems. They begin by showing that biology is able to be engineered, a point already proven by the many practicing synthetic biologists. One of the largest points they make is that the cell is in a dynamic environment. The cells themselves undergo evolutionary change, and the environments around them change. They then finish by saying that while this is a promising field, it is still new, and it is difficult to scale the work like other engineering disciplines.
• KPHershey 14:50, 19 February 2008 (EST)

Eyad Lababidi's Response

• Fast, cheap and somewhat in control
  • .This article has an interesting point of view because weve read before about how synth bio needs to turn itself into an engineering discipline, but no one ever really questioned if it was possible. The article makes really good arguements of what if its liek the wheather where its to complex to control. This may be the case considering were dealing with real life and evolution, if evolution was the cause to allow life to withstand centuries of time who says we can even contain it. This is important because the biggest problems we have with harnessing cells as a chassis is that they are living organisms that do their best to survive, not to best suite us and produce the arbitrary chemicals we want for circuits.
• A partnership between biology and engineering
  • The article examines the arguement that synthetic biologists make when they try to distinguish themselves from the rest of biology. While there are some good points about how names are sort of arbitrary, i believe theres something valueble in making it clear who you are and what your intentions are even in an engineering field. this is especially useful in situations of data that could be passed on to you or for applying for funding.
• Eyad Lababidi 17:06, 19 February 2008 (EST)

Patrick Gildea's Response

• A partnership between biology and engineering
  • This article explores the different outcomes that arise from applying principles of systems biology to synthetic biology. In short, systems biology concerns itself with the study of understanding the behavior of a biological ensemble, where the study is focused on the whole instead of individual parts. Obviously in synthetic biology we’re concerned with identifying individual parts and using them to build different parts to accomplish a certain function. It makes sense to combine knowledge from these two areas where the study of biological systems leads to understanding of the behavior/development of organisms which can benefit synthetic biology by forming parts out of organisms whose behaviors have already been characterized in systems biology. The paper does mention some project ideas that will have ramifications for the future such as design-based biological engineering resulting in the ability to program and execute multi-step synthesis and so on – kind of makes you want to do a project like the one I presented on last week right?

• Fast, cheap and somewhat in control
  • Again, this article discusses merging the discipline of engineering and biology. They prove that an engineering approach to biology, though unlikely at first, is succeeding through the evidence of research done by others that demonstrate that the cell is organized. Tools are being used to take advantage such as comparative genomics to uncover the structure and organization of the genome. However, the article does mention the challenges that surmount the field of synthetic biology such as the gene circuits and parasitic effects/cross-talk, the biophysics of reaction networks, and so on. In all, I think the most beneficial part of the paper for the VGEM team is the part that discussed the engineering challenges that discusses some of the issues that we have learned about in some more detail. For example, the discrete and stochastic behavior of chemical reactions in a cell; I have thought of biobricks as simply parts or lego bricks that have a certain function. Yet has anyone wondered about the interplay of chemistry between different biobricks from different genomes?
• Patrick Gildea 17:20, 19 February 2008 (EST):

Dan Tarjan's Response

• A partnership between biology and engineering
  • Roger Brent starts his piece by sifting through the variety of terms used to describe field which partially overlap in their activities. He finds an important distinction in synthetic biology's desire to use modeling to predict the outcome of a design before assembling anyhting physically. It's stated that the understanding and the tools to accomplish this goal are not present yet and need to be developed for the success of the synbio endeavour. Further he highlights the fact that synthetic biology will require an intersection of engineering and science such that both halves can inform the other. I agree and I think for a long while people working in what Brent sees as being synthetic biology will need to be part scientists and part engineers.

• Fast, cheap and somewhat in control
  • This paper discusses some of the roadblocks for synthetic biology to its destination of becoming an engineering discipline. The authors summarize the difficulties in creating parts and using them in non-native organisms. Further Arkin and Fletcher point out that great attention needs to be paid to mutation rates. Even just a natural mutation rate in yeast can lead to the degradation of a genetic circuit after only a few days. Circuit design can influence how fast mutations can disable its function (obviously). Gene circuits also need to be designed with consideration for noise which can vary in amplitude and type. The paper states that fortunately there seem to be paths that can be followed to overcome these obstacles. In terms of parts characterization, I think this will be a money and labor intensive process unless it could be automated or models are designed which can perform reliable predictions.
• Daniel R Tarjan 17:49, 19 February 2008 (EST)

George McArthur's Response

• A partnership between biology and engineering
  • Roger Brent's article is seemingly largely focused on terminology and definitions regarding systems biology. However, he makes it clear that synthetic biology and systems biology are two sides of the same coin in that synthetic biology can take advantage of the theories proposed by systems biology and these same theories can be tested by synthetic biology (a theme that will be revisited in detail when we talk about how systems biology can serve as a foundation for synthetic biology later on in the semester). Brent points out that the description of parts is simply anatomy and that physiology is the description of how these parts fit together in a functioning system. He suggests that this is the basis for approaching systems/synthetic biology. Synthetic biologists work towards designing and constructing biological systems from well-defined parts that are capable of complex behavior. However, there is "now no systems biology that [synthetic biologists] can use to predict the behavior of the systems they design." Interestingly, synthetic biology seems to be poised to make huge changes in the realm of biological engineering but is forced to wait for new, powerful technolgies to push it along (e.g., computer-aided design tools). Once this takes place, manipulation of biological parts will likely change the world forever, just as manipulation of the electron did.
• Fast, cheap and somewhat in control
  • Arkin and Fletcher point out some real obstacles in the development of synthetic biology in this article. Driving forces such as energy and environmental problems seem to be pushing biological engineering toward a synthetic biology approach (i.e., applying true engineering principles). Isolated projects in one field could help advance projects in another, rather than being special cases. It's interesting that the very thing that disturbs biological system design, evolution, can also be used as a very powerful design tool (see my notes on "Directed evolution of a genetic circuit"). Despite the pitfalls of evolution, biological systems are naturally modular and can therefore be engineered in a modular fashion. We now have available to us a vast amount of data regarding the molecular workings of cells. This will enable intelligent system design. This is what sets synthetic biology apart - it formalizes the process of designing biological systems. Some major obstacles to overcome, however, include the establishment of a DNA synthesis infrastructure, an easy assembly process, and a way of predicting part functions (i.e., a simulator). More work is required to further develop the field, especially in relation to computational biology (used for both analysis and design), measurement/characterization standards for parts (especially regarding their interoperability), and streamlined chasses (e.g., minimal or synthetic genomes/cells). These are all very important areas in which the VGEM Team should investigate.
• GMcArthurIV 22:33, 19 February 2008 (EST)

George Washington's Response

• A partnership between biology and engineering
  • This article attempted to clarify the difference between synthetic biology and the other molecular biologies by emphasizing the goals of the field. In contrast to other biologies, synthetic biology does not just wish to divine truths about biological systems, but to have predictive power, such that given a set of DNA, or macromolecules, or even a full system of biological parts, one could simulate its predicted evolution without having to set up any direct experimentation. Even if systems could be designed under the other frameworks, synthetic biology permits a much broader scope. Much of the article seemed more semantic in nature, heavily emphasizing how terms should be defined, and so it seemed somewhat pedantic. I enjoyed the analogy of all the clock pendulums in New England as a 'bad' system, but there wasn't much new in the article. Although, I liked the emphasis on using synthetic biology to design completely new things that nature has never done before, as I really see that as the future of the field. Hijacking mechanisms already in place is certainly effective for many things, but new systems must be built from the ground up to really see the potential of the field.

• Fast, cheap and somewhat in control
  • This article touches on a couple of the challenges facing synthetic biology, as well as what progress has been made to understand and characterize their effects. It brings up evolution into undesirable strains and noise as two prominent issues in the field and shows how each of these can qualitatively change the behaviour of biological systems. It also addresses the question of whether a field as complex as biology can ever truly be engineered, but with an optimism nearly ubiquitous in the field. Most of the points in the article had been seen before, although its observation of various noise distributions having radically different effects was interesting. The main useful thing I gathered from the article was that if we are to create a circuit that will be useful for extended periods of time, we will have to go to great lengths to protect it against mutations that would render it inoperative.
• George Washington 03:25, 20 February 2008 (EST)