Synbio 2007

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Implications and Applications of Synthetic Biology

General Info

Contents

Spring 2007

Instructors: Jay Keasling

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

Tentative Schedule

Course Modules:

  1. Introduction to Synthetic Biology
    • 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.
    • 2/9 Jay Keasling
    • 2/9 Design of Tumor-Killing Bacteria - John (Chris) Anderson

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 on the 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 the discussions should touch on issues in ethics, policy, business, in adddition to science when applicable.

  • Lecture 1/19 - no discussion
  • Lecture 1/26 - no discussion
  • Lecture 2/2 - no discussion
  • Lecture 2/9
    • Introduction to Synthetic Biology #1
      • A Synthetic Oscillatory Network of Transcriptional Regulators [[1]]
      • Foundations of Engineering Biology [[2]]
    • Seminal Works in Synthetic Biology #2
    • Metabolic Engineering
      • Metabolic Engineering for Drug Discovery and Development [[3]]
      • Engineering Yeast Transcriptional Machinery for Improved Ethanol Tolerance and Production [[4]]
    • RNA in synthetic biology
      • Programmable ligand-controlled riboregulators of eukaryotic gene expression. [[5]]
      • Engineered riboregulators enable post-transcriptional control of gene expression. [[6]]
      • RNA in Synthetic Biology (Review) [[7]]
    • Protein Engineering
      • Computational Design of a Biologically Active Enzyme [[8]]
    • BioBricks
      • BioBricks to help reverse-engineer life [[9]]
    • BioBricks Website [[10]]. 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.
    • Ethics in Synthetic Biology
      • Synthetic Biology 2.0 Declaration [[11]]
      • Synthetic Biology: Navigating the Challenges Ahead [[12]]
    • Business and Synthetic Biology

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?

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