Week 1 HW: Principles and Practices

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Week 1: Principles and Practices

Class Assignment

1. Application or Tool to Develop & Why

Application: “The Bio-Puzzle” – A hardware-agnostic DNA assembly toolkit using split-protein reporters (e.g., Split-GFP) as physical “checksums” for long-sequence construction.

Why: For students and DIY biologists, the most immediate “biosecurity” threat is unintentional human error. Assembling long DNA (2,000bp+) from short, affordable oligo pools is difficult and error-prone. Currently, verifying these assemblies requires expensive and slow sequencing. The “Bio-Puzzle” transforms biosecurity from a restrictive policy into a helpful engineering tool. By engineering DNA fragments to produce a visual signal only when assembled in the correct order, we provide a real-time, “at-the-bench” verification system.

2. Governance/Policy Goals

Goal: To foster a culture of “Integrity by Design” in decentralized research environments.

  • Sub-goal A: Minimize human error in DNA synthesis by providing immediate physical feedback.
  • Sub-goal B: Establish a community norm where long-sequence assembly is inherently linked to transparency and verification.

3. Potential Governance Actions

  • Option 1: The Split-Reporter Standard (Technical): Standardize “Verification Tags” at DNA junctions.
  • Option 2: Orthogonal Overhang Library (Policy): Create open-source library of “puzzle teeth” for safe connection.
  • Option 3: The Bio-Cookbook Ledger (Social): Peer-verified platform sharing success outcomes.

4. Scoring Governance Actions

Does the option:Option 1Option 2Option 3
Enhance Biosecurity
• By preventing incidents112
• By helping respond321
Foster Lab Safety
• By preventing incident112
Protect environment
• By preventing incidents112

(1 = Best / 3 = Worst)

5. Prioritization, Trade-offs, and Ethics

Prioritization: I prioritize Option 1 (Split-Reporter) because it addresses the core technical challenge.

Ethical Reflection: This project shifts the focus from “top-down censorship” to “bottom-up empowerment.”

Assignment (Week 2 Lecture Prep)

Homework Questions from Professor Jacobson

    • The error rate of polymerase is $10^{-6}$.
    • The length of human genome is $3.2$ Gbp.
    • Biology utilize proofreading and mismatch repair to deal with this discrepancy.
    • The average length of a human gene is about 1,036 bp.
    • Total possible DNA sequences: $3^{345}$.

Homework Questions from Dr. LeProust

  1. Phosphoramidite method: Deprotection → Coupling → Capping → Oxidation
  2. Limit: Once it exceeds 200 nt, it becomes difficult to separate and purify.
  3. Yield: Decreases exponentially with length.

Homework Question from George Church

  • Essential amino acids: Lysine, Histidine, Isoleucine, Leucine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, Arginine.
  • Lysine constraint: Lysine can be supplied externally, so the constraint isn’t absolute and could undergo reversion mutations.