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CHE.496: Biological Systems Design Seminar


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Foundational Technologies

  • Discussion leader: Dan Tarjan

Thaddeus' Response

Drew Endry's article "Foundations of engineering biology" focused on the basic steps that synthetic biology will need to take in order to become a successful and applicable field. Currently, every project in synthetic biology is more of a research project than an engineering project. With the advances in DNA synthesis and recombination the field is ready to become available to a much wider range of workers and projects. In order to transform synthetic biology into a process that can be executed in a timely manner by anyone with minimal training several steps will need to be taken. First, the field will need to be standardized. Designers find it difficult to transfer the systems and information generated by other work groups to novel applications because a rigorous system of standardization has yet to be applied to the field of biology. The library of biobricks are a positive step towards standardizing synthetic biology. Decoupling is another engineering approach that would expedite progress in synthetic biology. Decoupling is the process of dividing a complex problem into simpler problems. Decoupling applies both to the type of work a biologist would do, design versus fabrication, but could also be applied to break designers into more specialized fields so that each designer would have a narrower more manageable problem to solve. Endry suggested that abstraction would be a useful technique for dealing with biological complexity. Abstraction could be used to organize the field into more manageable hierarchies of complexity. Another application of abstraction would be to fabricate biological parts entirely from scratch rather than relying on natural precursors so that they are easier to characterize. The most interesting part of the article to me was the description of synthetic biology as an attempt to remove the basic precepts of the biological systems we are working with. The three main factors which drive natural biology are complexity and diversity which couple to form evolution. Seemingly if perfect standardization and simplification occur the fourth problem of evolution, that the article mentioned but did not offer a remedy for, will fix itself because the mechanisms for evolution will be removed. I think the article offers an interesting idea for our VGEM project. Evolution was offered as a problem to synthetic biologists. A project could be devised however that harnessed evolution in less characterized systems. If the product of an optimized biological machine were set as a selectable marker conditions could be set that would hopefully select for those cells which have the best machine in place and also have the other properties which allow the machine to operate at a optimum level.

Brown's article about the iGEM competition is essentially discription of the history and mechanics of the competition. The most important part of the article for our concerns is the description of the biobricks and the standard registry. We will be using these bricks in our project and will need to learn to use and understand them.

Thaddeus Webb 02:26, 12 February 2009 (EST)

Joe Bozzay Response

  • Foundations for Engineering Biology:
    • The case is clearly made that synthetic biology holds great potential and is being driven by biologists, chemists, and various types of engineers. However, the systems engineering is still an expensive and unreliable process, mainly due to the complexity of biological systems and the lack of an engineering approach to simplify the problem. The inability to manage this complexity, inherent error in system design, variation of behavior in biology, and evolution pose four unique challenges to the field of synthetic biology. However, the standardization of functions similar to those found in engineering fields would no doubt increase the effectiveness of engineering systems biology. The lack of standards contribute to the enormous costs retained in the field and prevent efficient communication between the various communities. Taking an engineering approach, the breaking down of a complicated problem into manageable smaller problems (decoupling) would allow for multiple specialists to be working on various aspects of a problem, with standardization increasing the quality of communication. The abstraction of signals or system characteristics would allow for better system prediction. The integration of foundational technologies that enhance biological engineering will require leaders to encourage contribution from all the communities.
  • The iGEM competition: building with biology:
    • The iGEM competition allows students from various fields of study to come together and advance systems biology through learning. The use of specific standardized parts allows for an open design project that shows how simple biological systems can be built from interchangeable parts even though the field of biology is so complex. BioBricks are defined DNA sequences of specific structure and function that allow incorporation into living cells in order to construct biological systems. They function as interchangeable parts and can be assembled together through a ‘standard assembly’ process. BioBricks provide the advantage of abstraction and standardization, key engineering principles which will help increase the effectiveness of systems biology. The information on each BioBrick is stored in the Registry of Standard Biological Parts. However, the Registry does not contain the most accurate information on various bricks and well-characterized, accurate parts are hard to find. iGEM boasts more than 60 teams and the competition allows for students to use cutting edge research to solve new problems.

Joe Bozzay 03:02, 12 February 2009 (EST)

Rohini's Response

The main idea in Drew Endy’s article, “Foundations for engineering biology”, is that “synthetic biology” seeks to combine a broad expansion of biotechnology applications, with an emphasis on the development of foundational technologies, to make the design and construction of engineered biological systems easier. The author recognizes that the large number of unique functional components combined with unexpected interactions among components (especially evolutionary) makes it hard, at this time, to reliably engineer the behavior of complex biological systems. In other words, perhaps, we do not yet know enough about biological systems, or that biological systems are too complex to reliably engineer, or both. The author expounds on the need for standards and applying decoupling and abstraction strategies when conducting research in the “synthetic biology” field. There is a lack of standards in biological engineering everywhere from definitions, descriptions, and characterizations of components within the biological systems. By decoupling approach, a complex problem can be broken down into many simpler problems that can be tackled one at a time and combined at a later stage. By using the abstraction strategy, individuals can work at a single level of complexity within a biological system while paying little attention to details that define other levels. This way, the complexity of the system can be managed and there can be limited exchange of information across different levels of the entire system. The interesting point(s) of the article are the author’s rightful recognition of the “synthetic biological systems” as a complex, interdisciplinary, and challenging research area driven by at least four different groups: the biologists, the chemists, the ‘re-writers’ and the engineers. The author succinctly provides his personal understanding of how each of the fore mentioned groups approach “synthetic biology”, e.g., for biologists—it provides a direct and compelling method for testing our current understanding of natural biological systems; for the chemists—biology is chemistry and is thus a natural extension of synthetic chemistry with the ability to create novel molecules and molecular systems; for the ‘re-writers’—“synthetic biology” provides an opportunity to test the hypothesis that the genomes encoding natural biological systems can be ‘re-written’ leading to production of engineered surrogates that might supplant some natural biological systems; and finally, for the engineers—“synthetic biology” is a technology building upon past work in genetic engineering. Based on the information in the subject article and the second paper provided by the instructor, namely, “iGEM Competition: Building with Biology”, the concept of biobricks can be applied to the 2009 VGEM Team Project. We can further explore the idea of building with biobricks, because these “standard interchangeable parts” can be studied more closely specifically with the insertion in living cells. They are analogous to the “plug-and-play (PNP) components” technology that was developed a few years ago for the computer hardware components—which has been extremely successful. I think it is pretty fascinating how we can use biobricks to essentially program living organisms.

~Rohini Manaktala

Patrick Gildea's Response

  • The iGEM competition: building with biology:
    • The article introduces the iGEM competition and what synthetic biology is in general – the engineering of biological organisms. Biobricks are modular biological components of organisms, in other words genes that code for a specific function such as a fluorescence protein or a biological circuit. The cool thing about biobricks is that they introduce a level of abstraction to the structure of biological organisms. The ideal goal for biobricks is to build a library with different biobricks with different purposes such as reporters, biological chassis, and so on. A biobrick designer does not necessarily need to understand the minutia of biological processes in order to construct a plasmid for use in a biological organism. This is why the iGEM competition continues to attract interest from high schools with advanced biology programs. This past iGEM competition, there was a category in computational tools for more advanced design and modeling of the behavior of organisms.
  • Foundations for Engineering Biology:
    • Again, the article describes what synthetic biology is in terms of those with backgrounds in biology, chemistry, and engineering. For engineers – synthetic biology is a technology that builds up on past work in genetic engineering. The author of the paper, Drew Endy, states that for engineers, “synthetic biology has … an emphasis on the development of foundational technologies that make the design and construction of engineered biological systems easier”. I don’t quite agree with this statement since there is research and development in areas of biotechnology where the focus is not on developing foundational tools to advance the understanding and control of biological organisms. Rather engineers seek solutions to problems with the tools that they have. For example, there are researchers developing a biofilm in order to detect explosives and replace the need for bomb-sniffing dogs, which are expensive to train and care for. The issues of standardization, decoupling, and abstraction are discussed in this paper. These are powerful tools that will further the success of synthetic biology. In particular is standardization, which would allow for accurate characterization of biobricks uploaded to the registry. In other words, standardization consists of the: definition, description and characterization of the basic biological parts, as well as the standard conditions that support the use of parts in combination and overall system operation. Without standardization, there would be no registry and the design of biological organisms would be far more difficult.
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