Synbio 2007

Implications and Applications of Synthetic Biology

General Info

Spring 2007

Instructor: Jay Keasling (keasling@berkeley.edu)

GSI: Jeffrey Dietrich (jadietrich@gmail.com)

Logistics: Lecture/Discussion: 2 hours, 10-12 AM Friday

Grading:

• Literature Review 30%
• Group Project 60%
• Class Participation 10%

Office hours: contact Jeffrey Dietrich to arrange a meeting

Announcements

• ASSIGNMENT (Due 2/16): email Jeff with your three top choices for topics to lead in literature review group discussion. If there is a topic outside of those provided you may list it as well.
• ASSIGNMENT (Due 3/9): email Jeff with your group project members and a 1-2 sentence description of your project.
• There are a number of areas in the Bears Breaking Boundaries competition that are related to synthetic biology, including designing an iGEM project and writing a white paper. The link to the site is: [Bears Breaking Boundaries 2007]
• The Feb 23rd lecture will be held at 717 Potter Street in Berkeley to accomodate our panelist's schedules. There are a number of different ways to get to Potter Street, included below:

1. Drive-there is a large parking lot, but you will need to get a temporary parking pass when you arrive to the building.
2. LBL Potter Street Shuttle. This picks up next to the Wells Fargo on Center Street at 9:20. You will need an LBL badge to get on the shuttle though
3. The #9 Bus. This picks up at the downtown berkely BART and you can get off at 7th and Anthony (Right next to Sharfenberger) and the Potter Street Building is a block to the west.

In any case, give Jeff a call (281-772-4475) if there are problems...plus I will probably be driving people down to Potter Street anyways.

Tentative Schedule

• 1/19 Introduction, Basis for Synthetic Biology - Jay Keasling
• 1/26 Modeling and Design of Synthetic Systems - Adam Arkin
  • Genetic models, stochastic and continuous simulations, adaption of circuit methods to SB.
• 2/2 Drugs from Bugs-Jay Keasling (Presentations and References)
• 2/9 Design of Tumor-Killing Bacteria - J. Christopher Anderson (Presentations and References)
• 2/16 James Carothers
• 2/23 Panel Discussion (George Church, Drew Endy, Jay Keasling) -- @ Potter Street (see above directions in the announcements section)
• 3/02
• 3/09 Jack Newman (Amyris Biotechnologies)

Literature Review Assignment

Every student will be required to lead one class discussion over selected readings/topics assigned for that week. Discussions are meant to last approximately one hour and will occur following conclusion of the day's lecture. Readings for that week's discussion will assigned, but discussion leaders are encouraged to contact the GSI if they find readings they feel are appropriate for that week's topic. If there are suggestions for different readings, please contact the GSI at least one week prior to the scheduled date so that the appropriate files can be uploaded to the wiki for class use. The format is of one's own choosing (powerpoint, chalk talk, class debate, etc), but should attempt to bring a number of different perspectives to the table. This class is multi-disciplinary, and where applicable the discussions should touch on issues in ethics, policy, and business in addition to the science.

• Lecture 1/19 - no discussion
• Lecture 1/26 - no discussion
• Lecture 2/2 - no discussion
• Lecture 2/9: Introduction to Synthetic Biology #1
  • Presenters: Sisi Chen, Jim Cheng, Arash Calafi (Presentations and References)
  • A Synthetic Oscillatory Network of Transcriptional Regulators [[1]]
  • Foundations of Engineering Biology [[2]]
• Lecture 2/16: Introduction to Synthetic Biology #2
  • Presenters: Jonathan Foley, Josh Kittleson, Emily Perttu, Lane Weaver
  • A bottom-up approach to gene regulation [[3]]
  • A synthetic multicellular system for programmed pattern formation [[4]]
• Lecture 3/02: Metabolic Engineering
  • Presenters: JT Koerber, Priya Shah
  • Media:Metabolic Engineering for Drug Discovery and Development.pdf
  • Engineering Yeast Transcriptional Machinery for Improved Ethanol Tolerance and Production [[5]]
• Lecture 3/09: Genetic Circuits
  • Presenters: Austin Day, Josh Hug, David Tulga
  • Genetic Parts to Program Bacteria [[6]]
  • Reconstruction of Genetic Circuits [[7]]
• Lecture 3/16: RNA
  • Presenters: Doug Brownfield, Eddie Wang, Virginia Zaunbrecher
  • Engineered riboregulators enable post-transcriptional control of gene expression. [[8]]
  • RNA in Synthetic Biology (Review) [[9]]
• Lecture 3/23: Protein Engineering
  • Presenters: Andrew chang, Ryan Shultzaberger, James Zhang
  • Computational Design of a Biologically Active Enzyme [[10]]
  • Fancy footwork in the Sequence Space Shuffle [[11]]
• Lecture 4/6: BioBricks
  • Presenters: Lauren Miller, Joe Peltier, Derrick Speaks
  • BioBricks to help reverse-engineer life [[12]]
  • BioBricks Website [[13]]. Students, please familiarize yourselves with what content can be found on the website. Discussion leaders, please provide a tutorial on how one could use the website.
• Lecture 4/13: Ethics in Synthetic Biology
  • Presenters: Greg Davis, Jill Fletcher, Marisa Harano, Anthony Stavrianakis
  • Synthetic Biology 2.0 Declaration [[14]]
  • Synthetic Biology: Navigating the Challenges Ahead [[15]]
• Lecture 4/20: Business and Synthetic Biology (articles to be posted shortly)
  • Presenters: Jeff Chen, Gondica Nguyen, Ziv Shafir

Group Project Ideas

1. Dual-use strategies: Identify a synthetic biology “platform” or product with “dual-use” applications for both developed and developing country markets
2. Energy: What is the energy balance of proposed schemes to produce biofuels from genetically-engineered organisms? What are the relevant technical targets that would need to be met for bioenergy to make sense from an economic and thermodynamic point of view?
3. Marine biotechnology: Marine natural products represent a largely untapped and promising resource for drug development. As scientists with the Harbor Branch Oceanographic Institution observe:

The marine environment may contain over 80% of the world's plant and animal species, and during the past decade over 5000 novel compounds have been isolated from marine organisms. The diversity of chemical compounds in the marine environment may be due in part to the extreme competition among organisms for space and resources … It is hypothesized that sessile marine organisms (for example, sponges, octocorals, tunicates and algae), have developed a diverse array of chemical compounds known as "secondary metabolites" or natural products for defense and competition.

It is worth noting that this research group alone has discovered 235 bioactive compounds and has had over 117 patents issued over the last 10 years.

Researchers in synthetic biology may be in a position to increase the payoff from this research. Once pharmaceuticals (or possibly specialty chemicals) have been derived from marine natural products, “synthetic biology” approaches developed at Berkeley could lower the cost of producing them at high volumes. This, in turn, would increase the economic and social value that we place on marine biodiversity, in addition to its incalculable intrinsic value. Potential projects:

a. Develop a list of the most promising pharmaceuticals, specialty chemicals, etc. that could be biosynthetically derived using genes from marine organisms. Identify current stage of commercialization. [Examples discussed in the literature include: a cancer therapy made from algae; a painkiller derived from the toxins in cone snail venom; anti-viral drugs Ara-A and AAZT and anti-cancer agent Ara-C developed from a Caribbean coral reef sponge; and Dolostatin 10 (extracted from an Indian Ocean sea hare and undergoing clinical trials for the treatment of breast cancer, tumours, and leukemia. A publication called Natural Products Report has review articles on marine and other natural products. See http://www.rsc.org/Publishing/Journals/NP/index.asp

b. Determine whether any of these are candidates for cost-effective biosynthesis using existing platforms (e.g. pathways for isoprenoids)?

c. Does an analysis of possible high-value marine products for biosynthesis suggest new pathways that would produce precursors for a broad range of them?

d. What models exist to re-invest some of the revenue generated from marine products into marine biodiversity efforts?

Group Project Information

Each group will consist of 3 or 4 people and will hand in a 10-15 page (before the addition of figures) on the last day of class. The report should be single spaced, font size 12, 1-inch margins. Each group will also give a 10-15 minute presentation about their project during one of the final discussion sections.

There are three optional formats for this paper, and is dependent on the approach taken for the project: scientific, policy, or business. Because each format necessitates different information, there are slightly different requirements for each. In all cases, however, students should focus on a topic in synthetic biology (as opposed to what would just be classified as metabolic engineering, etc.). When writing, think about the definitions of synthetic biology that Dr. Keasling, Dr. Arkin, and others have provided in the class.

Email Jeff with your project groups and a 1-2 sentence description of your project by March 9, 2007.

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Scientific/Engineering Approach

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The format for this approach will be in the style of a grant proposal. Papers should address at least, but are not limited to, the following:

1) Give a brief overview of the project idea.

2) Discuss past or existing research related to your idea.

3) What is the purpose/goal of your idea? What are the long term applications/implications of your project/paper/plan?

4) How would you go about trying to achieve your idea? Discuss experimental protocols or how you would develop platform technologies to test/build your idea.

5) Discuss what parts of your project will be hardest to achieve, and propose alternative strategies in the event of setbacks.

6) Discuss the timeframe required to achieve your project. Feel free to provide milestones - try to be realistic. Could your project be achieved with existing technologies or would you require new technologies (which may extend the time required to achieve your idea)?

7) What are the ethical/social issues/impacts of your idea (if applicable)?

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Policy Approach

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The format for this approach will be in the style of a white paper. Papers should address at least, but are not limited to, the following:

1) What is the problem with a given technology?

2) What are the current policies in place? Are the policies self-imposed or are they state, nationally, or internationally imposed?

3) What are the short- and long-term implications of maintaining the status quo?

4) What are your policy recommendations?

5) Who would the recommendations be proposed before (National Academy of Sciences, Congress, etc.)? Justify why you decided to take this route.

6) What do you predict the effect of implementing the policy recommendations will be?

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Business Approach

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The format for this approach will be in the style of a business plan to be pitched before venture capitalists. Papers should address at least, but are not limited to, the following:

1) Market Definition. Think about the size of the market, the consumer, as well as current competitors.

2) Market Trends. Where is the market going to go in the future; think along the 10 year timeline that most venture capitalists follow.

3) Description of the technology. What progress has been made thus far in the developmnt of the technology?

4) What intellectual property does your group possess surrounding the technology (or what would you patent - if the technology has not yet been developed fully)

5) Provide a timeline (10 year) for your company and what products you see being developed

6) What is your exit strategy

7) Provide a hypothetical balance sheet justifying how much capital you will need to cover your future expenses

8) Logistical information on your company: how many employees, who are the executives, what type of facility is required.

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If a group is unfamiliar with a particular approach format do not hesitate to contact Jeffrey Dietrich to obtain examples.

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