Virginia United/2010/Readings/Responses/UVA/Assignment1

Assignment 1 Responses (Due Jan 25)

Example:

• Paper title
  • Response
• Paper 2 title
  • Response

Daniel R Tarjan 21:29, 24 January 2010 (EST)

Building outside of the Box: iGEM and the Biobricks Foundation

Main points:

• Creating an open sharing platform of DNA constructs
• Building a Registry of biobrick parts
• Developing tools to make engineering biological systems easier (BBF & iGEM)

IGEM:

• Synthetic biology competition held at MIT
• Teams identify a real world problem and prototype engineered genetic programs as possible solutions

Synthetic Biology:

• Relies on the decoupling design
• Uses abstraction to manage biological complexity
• Limitations:

1) Budget for de novo DNA synthesis -solution: share and reuse parts,Registry of parts 2) Challenges with gene synthesis -solution: optimize variable copy number vectors with enhanced transcriptional insulation 3) Too much time spent trying to understand how systems work -solution: abstraction hierarchy

Registry of Parts:

• Online catalog of parts
• Purpose-streamline a process that can be used to make the integration of parts more reliable and efficient
• iGEM competition fosters a quality control check by rewarding teams that contribute parts and improve technical standards

Biobrick Foundation:

• Provide a legal framework for the collection of functional genetic elements encoding bio parts
• RFC (request for comment)
• Develop a contract between the inventor and user (determine terms of use,etc)
• Reduce legal ambiguity around use and re-use of parts—BPA (Biobrick Public Agreement)

Five Hard Truths for Synthetic Biology

Challenges in the field:

1) Many of the parts are undefined -eliminate variations arising from experimental conditions and instruments by measuring promoter activity relative to a reference promoter (standard)

2) Circuitry is unpredictable -cells integrate genes in their genome unpredictably -requires trial and error process -computational modeling can be used for predictions -optimize the system with directed evolution: mutating DNA sequences, screening their performance, selecting the best candidates, repeat the process

3) Complexity is unwieldy -speed up biobrick assembly with assembler cells, selection cells, enzymes

4) Many parts are incompatible -genetic circuits can have unintended effects on host -solution: develop orthogonal systems that operate independently of the cell’s natural machinery

5) Variability crashes the system -i.e. growth conditions, noise, genetic mutations

Rohini Manaktala 23:59, 24 January 2010 (EST)

Five Hard Truths for Synthetic Biology

1) Many of the parts are undefined -researchers find it unable to characterize all the parts within an engineered biological system -genes being introduced into the system work unpredictably in different configuration and conditions -most of the time, too complex to capture by standardized characterization

2) The circuitry is unpredictable -laborious process of trial and error -Reduce the guesswork by using computer modeling -directed evolution

3)The complexity is unwieldy Solution: -Automated process to combine genetic parts, which might involve assembly using "robots"

4)Many parts are incompatible

• 's Solutions:
• 's orthogonal systems that operate independently
• 's parallel systems which allow tweaking components without disrupting stability of the the biological system
• 's physically isolate the synthetic network from the rest of the cell

5)Variability crashes the system -Solutions: -Synchronize blinking by relying on cell-cell communication -Use more accurate DNA replication machine

Applications: bio-fuel production

Yong Y. Wu 16:28, 25 January 2010 (EST)