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Transformational Technologies for
Biology, Medicine, and Health
Honors 222B & MEBI 498A, Spring, 2013

Project #3:
Synthetic Biology -- CAD tools and Wiki-publications

Due Monday, May 24th, 5pm.

Building new living systems which do useful things is a new and transformational biological technology. "Synthetic Biology" is the most common name for the field of research that aims to engineer biological systems. Whether or not there is a precise definition, the field is rapidly growing. In May of 2010, the J. Craig Venter Institute published their work on synthesizing a complete genome, successfully introducing it into cells from another organism, and having that new synthetic organism continue to replicate (Gibson 2010).  This work spurred strong interest from the public, the media, and prompted President Obama to call on the Presidential Commission for the Study of Bioethical Issues to study the implications of synthetic biology research. (I've assigned the executive summary of their report for Week 7).

In this assignment, your interdisciplinary team will learn about a particular synthetic biological system (as described in the primary literature, see below), and produce a multi-faceted report about this system. The report will cover at least two viewpoints:

• Technical: The report must include a description of the system behavior, a specification of the DNA circuit design, and information about the biological context for this system (e.g., required organism, and any other biological requirements for functioning).
• Broader implications: This section should be designed for the "educated lay audience". It will cover aspects of the system such as potential signficance, future work, and implications for society (including ethical considerations).

There are several learning objectives in this project

• Learn in depth about one specific example of synthetic biology research
• Learn to work well in a multi-disciplinary team
• Learn about wiki publishing
• Learn about CAD tools

An important learning objective of this project is to learn to work in a multidisciplinary team. As sent out via email, I've divided the class into teams of 3-4 students that cover a breadth of expertise and backgrounds; each teammember should use his or her expertise to make the group’s report stronger.

Each team is assigned a primary-literature, cutting edge article that describes a synthetic biology system (see below). Your team must produce a report as a wikipedia-style web page that is useful to both synthetic biologists (i.e. as a technical summary of the work), as well as to an interested educated lay audience, who may be interested in the broader implications and potential uses of the technology. (Publishing your project on the actual wikipedia.org system is not required.) Team member must have specific roles -- i.e., some will focus on the technical, synthetic biology aspects, while others will focus on the "broader implications" sections of the report.

It is required that (a) you post all your deliverables to the course wiki web site (we have created a private, UW netID sandbox wiki that all members of the class can see and post to). This wiki page also includes a successful project page from 2 years ago for you to look at as a model of what I might expect (the project called "morphogen control"). It is also strongly recommended that you use CAD technology to understand, visualize, and represent the technical details of the selected paper. In particular, you should use the Tinkercell system; a CAD system specifically for engineering synthetic biology constructs. Thus, another role for the team will be to select one person to be the lead on the work to use Tinkercell to represent your synthetic biology system. (Note that for some papers, there may be an overwhelmingly large number of circuits that could be displayed via Tinkercell. You need not be exhaustive!)

Your reports must discuss broader issues around the use of living organisms as a technology. There is an important distinction between real current capabilities of a technology and discussion of its potential. The line between the two can become blurred as the popular press simplifies or exaggerates different aspects to better communicate, entertain, and captivate their audience. However, assessing real capabilities is critical to making educated decisions in research, investment, and public policy.

Doing the Work:
1. Read the assigned article and meet with your team to discuss it. The first checkpoint is for everyone in the group to choose a role: Technologist, Biology researcher, science writer,etc.
2. Start a wiki page on your group topic and write about your aspect of the project. Use the Wikipedia guidelines as a guide (Warning: These are extensive so it is well defined).
3. Send updates to instructors showing progress, (see Milestones, below) and respond to critiques provided by instructors.
4. Discuss your entry and your experience working as a team.

Papers: The four teams are designated by colors, below, find the papers, which are all posted under the single eRes link of "Synthetic Biology papers":

• Red Team: Logic gates:
  "Programmable single-cell mammalian biocomputers", Auslander, et al. 2013.
• Blue Team: Logic in E. Coli:
  "Synthetic circuits integrating logic and memory in living cells", Siuti, et al., 2013
• Green Team: Improving Taxol production:
  "Isoprenoid Pathway Optimization for Taxol Precursor Overproduction in E. coli ", Ajikumar et al., 2010.
  
• Yellow Team: Exploring homeostasis:
  "Modular Design of Artificial Tissue Homeostasis: Robust Control through Synthetic Cellular Heterogeneity", Miller, et al., 2012

The Eres library contains simple PDFs of these publications; however, most (all?) of these articles also include supplemental material available from the source journals (Nature, PLos, Science), and you should definitely download this material.

Milestones: For this project, I ask for 2 checkpoints prior to submitting the final version of your project:

1. Due May 13th: Read the paper, and send a brief description of what each person's contributions will be (describe your role on the team) .
2. Due May 17th: A rough draft of the wiki pages for feedack from me (by the 15th). All team members must contribute. Some sections may be in outline draft, but I should get some information for all components of the report.
3. Final submission due May 24th. This is in two parts: First, the wiki pages produced by the team, containing both the technical and the "broader impacts" sections. Second, an individual reflective report sent to catalyst about the learning experience. See below:

Requirements: The wiki pages you create must conform reasonably well to the WIkipedia guideline pages. In addition to the wiki pages (covering both technical & broader impacts), each team member must also report on their experiences with the project, the tools, and the team:

(a) Wiki: Technical aspects:
What is the behavior of the system? What is the DNA circuit design? Replicate this design using Tinkercell and create an imagemap for you wiki. What if a researcher wished to replicate this work--how much of the DNA sequence information is available? What is the biological context necessary to replicate the behavior (e.g., species and any other required biological conditions)?

(b) Wiki: Broader impact aspects:
Why is this device important? What potential does it have in solving larger problems? What are the next steps for this work, and in what direction do you think this research will go? What benefits and detriments might there be to society? With how much certainty can one even answer questions of societal benefits and detriments? What are the ethical implications of this work? What other related information resources or organizations might help to understand the context of the system?

(c) Reflective report: Project experience:
An important aspect of learning is self-reflection; in this report we ask that as individuals, you think back over what helped you learn (and what didn't!) Describe what worked well and what didn't -- did the team communicate well? Were the tools appropriate? Easy / hard to use? How did the team organize the work, and choose to organize the wiki pages? How well did the team problem-solve when challenges were encountered? Your reflective report must also include an assessment of the value of your individual role and contributions to the team. Although this portion of the project must be produced individually, you should also reflect as a team on what is working and what isn't -- tackling these problems well will help your overall product!

Extensions, going beyond the specs: As with most of the projects in this class, this is an "open" assignment. There are a variety of ways to go beyond the minimum requirements. For example:

• Use Tinkercell to also build an actual mathematical model and simulation of the designed DNA circuitry.
• Annotate the DNA sequence used.
• Take the next step and actually post your wiki pages to Wikipedia.org. You may need to broaden well beyond focusing on the single article to do this.
• Investigate who owns the system -- e.g., is there a patent?
• Investigate the cost of building. producing, and potentially selling the system.
  

Grading rubric:

Although unlikely to be dramatically different, different students on a single team may recieve different grades. In general, I plan to average the first three rows (see below) to get a baseline team grade, and then modify this up and down for individual grades (if I feel it's appropriate to do so at all) based on the reflective report and on the division of labor. In the table below, there are certainly ways other than what I list to acheive grades in the 3.8 - 4.0 range. The general idea is to go beyond the spec and to impress me with your understanding of the material and breadth and depth of your own research into the topics.

Last Updated:
May 1, 2012

Contact the instructor at: gennari@u.washington.edu