Keasling: Synthetic Biology Class

Implications and Applications of Synthetic Biology

General Info

Spring 2006

Instructors: Jay Keasling, Adam Arkin GSIs: Howard Chou, Yasuo Yoshikuni.

Logistics: Lecture: 2 hours, 8-10 AM Wednesdays Discussion: 1 hour per week date/time TBA

Grading: Group Project 90%, Class Participation 10%

Office hours: TBA

Tentative Schedule

Course Modules:

1. Introduction to Synthetic Biology
   • 1/17 Introduction, Basis for Synthetic Biology - Jay Keasling
     • Synthetic circuits, Elowitz' repressilator, foundations of genetic engineering, cloning. Enabling technologies: synthesis and sequencing.
     • Slides

1. • 1/25 Current Capabilities in Synthetic Biological Engineering - Keasling
     • Working Systems, iGEM competition projects, successes in artemisinin project.
     • Papers Questions

1. • 2/1 Modeling and Design of Synthetic Systems - Adam Arkin
     • Genetic models, stochastic and continuous simulations, adaption of circuit methods to SB. BioJADE design tool.
   • 2/8 Projects and Future Directions - Keasling
     • Artemisinin project, prostratin, and bio-energy.
2. Applications of Synthetic Biology
   • 2/15 Biological Energy Production, Tad Patzek
     • Current and future platforms for synthetic energy, economic and thermodynamics of energy production and distribution.
   • 2/22 JGI Termite Gut Project
     • Extracting and integrating cellulose digestion and assimilation parts from Termites for energy applications
   • 3/1 Pharmaceutical& Chemical Development and Discovery
     • Amyris will discuss the development of Artemisinin and related compounds, their discovery and commercialization approach.
   • 3/8 Marine Derived Compounds and Development - Harbor Branch Oceanographic Institute
   • 3/15 "Dual-Use" approaches
     • Pathway development for high-value products, and for easy, cheap deployment in the developing world.
   • 3/22 Final Project Planning and Discussions
     • Spring Break
3. Ethical, Legal and Policy implications of Synthetic Biology
   • 4/5 Steve Mauer (GSPP)
     • Open Source Biology & License models.
   • 4/12 Blue Heron
     • DNA Synthesis technology, government and self regulation of synthesis technology.
   • 4/19 Steve Block, Stanford, Rogert Brent, Molecular Science Institute
     • National security implications of genetically-engineered pathogens
   • 4/26 Tom Knight (MIT)
     • How can synthetic biology be harnessed for biodefense?
   • 5/3 Drew Endy (MIT)
     • What should a national strategy for Synthetic Biology look like?

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?