Synthetic Biology Paradigms, Part I

Is any one conceptual framework is sufficient for advancing the field of Synthetic Biology? Will a new paradigm be needed eventually? We can apply a diverse set of paradigms to think about how biology works: Analog devices (clocks, gears, etc) or digital circuits (processor), biochemical pathways where the flow of substrates can resemble the flow of fluids through a complex network of pipes, or even complex mathematical constructs (like those developed by Wolfram) can all be used to represent or draw parallels with different aspects of molecular biology.

Synthetic Biology is sometimes described as molecular biology with an engineering perspective. Indeed, many leading researchers in the field have backgrounds in electrical engineering or some related discipline. Much of the earlier work done by pioneering synthetic biologists has been to formulate biological phenomenon in more familiar engineering terms. These efforts has enabled engineers to leverage their expertise during the design of complex artificial genetic networks and cell behaviors. Are the promises of synthetic biology within our grasp, limited only by a need for the import of more engineering knowledge?

Despite the success of an engineering paradigm in synthetic biology, I believe that harnessing the full potential of this field will require new concepts and perspective. Synthetic Biology can and should grow from conceptual frameworks borrowed from engineering disciplines, but also must not be constrained by them. 

Incorporating ideas and concepts from fields other than the digital logic of electrical engineering can only serve to strengthen the efforts of a synthetic biologist. In this series of articles, I will detail how perspectives from Molecular Biologists, as well as Economists and other Engineers (particularly those that deal with Analog systems) may prove to be an invaluable part of the synthetic biologist's conceptual toolkit. The remainder of this article (which you can view by selecting 'Read More') details a recent advance in synthetic biology: the design of an analog genetic circuit by the Sarpeshkar Laboratory Group. I also discuss how Synthetic Biology can mimic and learn from nature, and why keeping an open mind and a flexible vocabulary may be important.

Paper of the Week at JBC

A stalled ribosome (Dark Blue) is rescued through translation of the tmRNA ORF (Magenta). Proper positioning of this region of tmRNA in the A-site is achieved by the C-terminal tail of SmpB (Yellow) which is connected to the body of the SmpB protein (Orange) by a flexible glycine residue (Yellow gymnast). Generated with PDB files 4ABR, 4ABS, and 3J18.

Although I usually don't use this blog to herald my own accomplishments (i.e. I didn't mention successfully earning my doctorate earlier in the year), I cannot hide my excitement that my first author article, "Active and Accurate trans-Translation Requires Distinct Determinants in the C-terminal Tail of SmpB Protein and the mRNA-like Domain of Transfer Messenger RNA (tmRNA)", has been selected for paper of the week.

As a paper of the week (an honor bestowed on less than 5% of all JBC articles, I am told), there is a neat summary of the article on the JBC site. The summary / synopsis piece is entitled "How Two Molecules Keep Ribosomes Moving". Along with this preview, there is also short profile about me.

Unfortunately, reading the actual, finished article requires a subscription to the Journal of Biological Chemistry. A word of caution to interested readers: it is written for an expert scientific audience (as almost all research articles for scientific journals are). However, it is possible to view the earlier, 'online' version of the article; in addition, the JBC capsule provides a bite-sized summary of the work.

The below is copied from the article page at the JBC website. Although I wrote most of it, I claim no copyright. You can find the original text at http://www.jbc.org/content/early/2013/08/28/jbc.M113.503896

Capsule

Background: tmRNA and small protein B (SmpB) rescue stalled ribosomes through a template switching mechanism.

Results: Changes to the SmpB hinge, SmpB C-terminus, or tmRNA ORF affect ribosome rescue activity and accuracy.

Conclusion: Proper positioning of SmpB and tmRNA make distinct and supplementary contributions to ribosome rescue.

Significance: Template switching requires concerted action of distinct SmpB, tmRNA, and ribosomal determinants.

A Blogroll for Synthetic Biology

The emerging discipline of synthetic biology holds tremendous potential for both basic research and for delivering powerful, novel solutions to real world problems (both in medicine and in other industries). This field has grown from a handful of researchers at Princeton, MIT, Harvard, and Universities in California (with pioneers such as Dr. Drew Endy, Dr. George Church and Dr. Ron Weiss leading the way) to include laboratories all over the world. It is my belief that this field will represent the future of biology and will be a vast and critical part of the economy in the years to come.

There are several great resources on the web to learn about synthetic biology and keep abreast of the latest developments. In addition to sites such as syntheticbiology.org, I present below a blogroll of great sites to visit for anybody interested in this amazing field. (Image above is modified from synthetic biology.org; I claim no rights to this image). Of course, I haven't included my own blog, even thought I already have several posts about synthetic biology (for example, my article about DNA synthesis)

My Top Three:

Oscillator

http://blogs.scientificamerican.com/oscillator/

Part of the scientific american family of blogs, Oscillator mostly focuses on Synthetic Biology and is a great resource for interesting articles and news about the field. I especially like some of the perspectives given by the main author Chistina Agapakis (whom you can follow on Twitter).

Peccoud Lab Journal Club Page
http://peccoud.vbi.vt.edu

http://peccoud.vbi.vt.edu/category/journal-club/

For the aficionado or seasoned expert, this is a great resource where recent papers about, or related to, synthetic biology are discussed. This is a great feature to have on a laboratory group website which deserves emulation by other scientists.

Dreamer Biologist's Blog

http://dreamerbiologist.wordpress.com/blog-2/

This blog, maintained by an undergraduate with a passion for biology (and synthetic biology in particular), features articles on a range of topics. He maintains a separate section with material solely devoted to synthetic biology (http://dreamerbiologist.wordpress.com/synbio/), and the title of the biology I think captures the essence of what this field is: a call for biologists to dream up novel solutions to real world problems, and imagine new technologies based upon the power of life.

Please continue reading the article to get my full list of synthetic biology blogs and sites (Click 'Read More'). They are really worth a read! 

Do you know of a blog or site that I have missed? Please share the link and a description below by leaving a comment.