CHE.496/2008/Responses/a9

Biological machines

• Discussion leader: George McArthur (Discussion guide)

Kevin Hershey's Response

• Designing Biological Systems
  • This powerpoint presentation by Pamela Silver of Harvard medical school discusses systems biology, which is different from the definition used in Che 496 thus far. In the powerpoint, she discusses the idea of standardizing biology and making it modular. The powerpoint goes on to say that systems biology can try to understand organisms, things we don't know, and why things work a certain way. She then goes on to discuss inelegant design, and points out the example of the vestigial thumb.
    • The review by Drubin et. al. discusses cell-to-cell signaling, signal transduction, and oscillations. This is an extensive article, but because of the delay in reading it, much of this has already been discussed (such as the Elowitz repressilator and Ron Weiss's stem cell research). However, this article ties everything together well.
    • KPHershey 15:41, 20 March 2008 (CDT)
• Biology by design: reduction and synthesis of cellular components and behaviour.
  • I was unable to load this document unto my computer. From the abstract, this article discusses the emergence of synthetic biology from the question, "how can I apply that knowledge to generate novel functions in different biological systems or in other contexts?" This is very prevalent in the iGEM participants, who use genetic parts from many organisms, standardize them, and combine them to create novel functions. While I was unable to download this document, I feel that the question it poses in the beginning is very relevant to the study of synthetic biology.
• KPHershey 00:46, 20 February 2008 (EST)

Eyad Lababidi's Response

• Designing Biological Systems
  • the power point was rather broad and i couldn't really get that much from it. We probably need to discuss the points she brings up about how evolutionary change is not planned out and does not necessarily run like a wheel oiled machine while human design we can skip intermediate steps? ya, I didn't really understand that statement. I do agree though that systems biology needs to understand the why and the how before necessarily trying to implement what we've got because without a good background its much harder to create anything useful. its almost like a short term solution versus spending the extra time on fundamentals so that in the long run we are much further on with what systems biolgy is capable of doing.
• Biology by design: reduction and synthesis of cellular components and behaviour.
  • This article i believe was just a long winded version of what we've been reading about since the beginning of the semester, although it was more encompassing then any one article weve read so far. It discusses how far synthetic biology has come along and where it needs to go and what processes the field needs to undergo to the there. The article also focused in more on the abstraction of synth bio to the level of systems and gives lots of examples and analogies like the robot to the e coli cell. although this article had some more indepth examples compared and i didnt know that cells could be wired up as the article showed.

Eyad Lababidi 12:56, 20 February 2008 (EST)

Dan Tarjan's Response

• Designing Biological Systems
  • This appears to be the slides which accompany a presentation. It deals mainly with the topic of conscious design versus systems that arise through evolution. It highlights the fact that certain things necessary for intelligent design of biological systems, like modularity in biological systems, are already present in nature. It then proposes that systems biology can work towards better understanding of (I'm assuming) gene circuits and other interactions within a biological system, intracellular and perhaps between cells also. ...Which is kind of what systems biology is about as far as I know.
• Biology by design: reduction and synthesis of cellular components and behaviour.
  • This paper is a thorough overview of the origins, current state of, and potential of synbio. It covers the technologies (DNA synthesis mainly) that enable researchers to fairly easily and more importantly in a deliberate fashion to modify existing biological systems or to restructure them. It goes over the current state of the field highlighting particular importnat achievements. Pattern formation is mentioned. This is worth mentioning because as the field of synbio progresses and its applications become more complex the techniques used to program and regulate the biological systems in question will have to grow congruently. The social implications of the field are also mentioned and they will no doubt become more important as the field grows and enters the lime light. I think the references cited in this article will be worth pursuing for further information about the details of certain projects mentioned in the paper.

Daniel R Tarjan 15:07, 20 February 2008 (EST)

Patrick Gildea's Response

• Designing Biological Systems
  • This powerpoint goes over what systems biology is and its goals – to understand evolution-based design strategies among other things. I think the main benefit (and only benefit) is the descriptions (albeit, short ones) of different parts, biological devices, the bacterial edge detector, and the synthetic biology counters. These are applications that we could possibly apply toward our project and these are part of the ethos that synthetic biology presents. A distinction is made in the powerpoint between rational and thought-out engineered design and inelegant design – trial and error kind of research that is simply abhorring to us engineers.
  • Edited Version for PDF article
    • The gist of the article was focused on describing the major accomplishments undertaken in biological systems design (aka synthetic biology); with an sidenote on the registry of biological parts (standardization) and what is being done in education to further research in this field. Synthetic oscillators and switches were mentioned – namely the repressilator and toggle switch (of which we have already read about) and the positive feed-back loop and an anti-switch. Perhaps we could design a negative feed-back loop? This type of switch seems more interesting to me because it is an inducer-concentration graded response instead of all or nothing types of switches. It seems that the type of switch here is a promoter that is in charge of its own synthesis of inducer. One other part of the paper that I found interesting was its section on metabolic pathway engineering. I found interesting the different ways where pathway engineering is used to develop a strain of food that contains nutrients otherwise not found in its wild variety (eg. The golden rice) but the advent of Monsanto Corp. probably makes this a short-lived goal for ending world hunger or at least malnutrition. I’ve been thinking of metabolic engineering using synthetic biology in the terms of manufacturing drug precursors (i.e. artemisinin) so much, that it is nice to see an application that utilizes metabolic engineering in a different manner.
      • Patrick Gildea 16:08, 18 March 2008 (CDT):
• Biology by design: reduction and synthesis of cellular components and behaviour.
  • This article mainly goes through what synthetic biology is as well as the foundational technologies that push the development of this field. As well as early applications made in synthetic biology and the challenges surmounted in those applications; also, future directions and considerations in synthetic biology were mentioned. All in all, we have already learned the “what is synthetic biology” and also that of the foundational technologies that drive the field (i.e. DNA synthesis, etc.). I think the most beneficial part of the article is both the sections on design and optimization of parts, modeling-guided circuit engineering, and the big section covering applications. In addition to the research mentioned in the design and optimization section (i.e. the Smolke group; etc.) an important point was raised in that the circuit engineers of the future will not only be limited to a catalogue of known parts, but also will have the ability to supplement natural parts with custom made parts – how many electrical engineers can say the same about complex circuits? Furthermore, regarding the section on modeling-guided circuits – Box 1 is a really good outline for designing gene circuits and I think this will be especially useful to us later when we actually design our biobricks. On the last section, I think that the different applications presented pose good ideas that can be advanced from the research already done and presented in that section. For example, I was thinking about using plant cells that have chloroplasts to create complex molecules instead of taking advantage of the metabolic pathway, is it possible to take advantage of the pathway inside the chloroplasts to directly govern the enzyme reactions in there as opposed to elsewhere in the cell? I know this may be similar to what the team did last year and other teams but what I really mean by complex molecules is something like artemisinic acid or something like that that is completely different than manufacturing butanol or something like that.
• Patrick Gildea 17:03, 20 February 2008 (EST):

George Washington's Response

• Designing Biological Systems
  • This was a fairly short PowerPoint presentation that would have been better with associated talking notes. The main aim of the presentation seemed to be that Systems Biology needs to change its focus from just developing systems ad hoc to a more methodical system, reminiscent of the standards used in the engineering disciplines. This is compatible with the aims of Synthetic Biology, so it seems Silver was pushing a transition to this field. She gave as examples several successes of Synthetic Biology, including the repressilator and the toggle switch and mentioned why man-made systems can, in principle, be far superior to any natural system; we are not limited to functional intermediates, but can make huge leaps in design at once. These functional intermediates often limit evolution, as demonstrated by the "inelegant design" concepts Silver shows, including the position of the trachea in front of the esophagus and the kludginess of the panda's thumb. Some of these examples probably would have been clearer had we more than just the PowerPoint. The main thing I took away from this article was the emphasis on being able to circumvent natural evolution by making these leaps in genetic design; Synthetic Biology is theoretically capable of so much, we should never limit ourselves in our eventual goals. We will, eventually, beat Mother Nature at her own game (unless we mess up and kill ourselves first >.<).
  • Designing Biological Systems redux - the PDF
    • This article was an excellent review of the progress thus far in synthetic biology. It touches on recent advances in effective switching, cell-cell communication, transduction pathway manipulation, metabolic engineering, biosensors, and cell minimization. In short, it accurately describes a very large portion of the current state of the field. It also discusses advances in DNA synthesis as an enabling tool for future research. The article seemed fairly comprehensive, so is useful as a reference in general. There wasn't much in particular that I felt we could use in our own project from it, except the numerous examples cited from elsewhere that we may include as elements of our design. However, I see this article as more of an index, a brief review of what is possible in synthetic biology and where to go to find out more about any specific technique.
  • George Washington 12:33, 20 March 2008 (CDT)

• Biology by design: reduction and synthesis of cellular components and behaviour
  • This wordy article discussed several examples of Synthetic Biology as used in the field. It seemed to touch briefly on a large number of topics rather than covering any one particularly in-depth, but this overview of the field was nice in that it described the Synthetic Biology process from start to finish, from inspiration to production. I liked its description of the microchemostat and its use in studying small populations of cells. I feel that could potentially be very useful if we need to examine cultures over relatively long time periods with little evolution. It touched on some of the benefits and problems involved with standardization, how having parts heavily characterized in certain operating conditions will aid modeling in those conditions greatly while potentially giving false impressions about applicability outside that domain. I feel this is extremely important and that in developing these standards, we as a field attempt to expand our findings as broadly as possible before moving on. Without data over broad operating conditions, much of this is not nearly as useful as it could be in the field. We should stay abreast of the literature and be aware of the techniques at our disposal, as well as the holes in the knowledge base, if we wish to significantly contribute to the field. I believe this is entirely possible.
• George Washington 21:00, 20 February 2008 (EST)