Week 1 HW: Principles and Practices

1. Biological Engineering Application / Tool

Idea: Low-cost, field-deployable waterborne pathogen detection kit for rural and urban areas in South Asia.

Why:

• Waterborne diseases like cholera, typhoid, and hepatitis A are major health challenges in South Asia.
• Current testing infrastructure is centralized, expensive, and slow.
• A portable, easy-to-use kit allows local health workers to identify contaminated water and prevent outbreaks.

Conceptual Design:

• CRISPR-based or colorimetric paper-strip detection.
• Results in under an hour.
• Data can be uploaded to a mobile app or cloud system to track contamination hotspots.

2. Governance / Policy Goals

Big Goal: Ensure the tool contributes to a safe, ethical, and constructive future.

Sub-goals:

1. Safety and biosecurity: Prevent accidental exposure from the kit.
2. Accessibility and equity: Make the kit affordable and usable in rural areas.
3. Data privacy and trust: Ensure digital results are handled ethically and securely.

3. Governance Actions

4. Scoring Governance Options

5. Recommendation

• Prioritized Action: Combine Option 1 (biosafety protocols) and Option 2 (funding & certification).
• Reason: Field safety is essential, and support ensures the tool reaches communities most in need.
• Trade-offs: Training and strict safety may slow deployment; funding dependency is a risk.
• Assumptions: Users follow instructions; regulatory bodies provide support.

6. Ethical Reflections

• Ensuring accessibility without creating dependency on NGOs.
• Balancing data transparency for outbreak tracking with privacy.
• Addressing cultural or social barriers to adoption.

Proposed governance actions:

• Standardized training programs and consent for data sharing.
• Community engagement to build trust.
• Open-source documentation to ensure understanding of the tool.

Week 2 HW: DNA Read, Write, and Edit

Professor Jacobson

1. Polymerase and error rate

Nature’s machinery for copying DNA is DNA polymerase. The error rate of typical polymerases is approximately 1 in 10^{4 to 10}6 nucleotides depending on the enzyme.

• The human genome is ~3 billion base pairs (3 × 10^9 bp).
• Without correction, polymerase errors would result in thousands of mistakes per genome replication.
• Biology solves this via proofreading and mismatch repair mechanisms, which reduce the effective error rate to ~1 in 10^9 bp, ensuring accurate genome replication.

2. Coding DNA for human proteins

• On average, a human protein has ~300 amino acids.
• Each amino acid can be encoded by 1–6 codons (degeneracy of the genetic code).
• There are theoretically many different DNA sequences that could code for the same protein.
• In practice, not all codons work equally well due to:
  • Codon usage bias (some codons are translated more efficiently)
  • mRNA secondary structure affecting translation
  • Regulatory sequences overlapping coding regions

Dr. LeProust

1. Most commonly used method for oligo synthesis

• Solid-phase phosphoramidite synthesis is the standard method.
• Nucleotides are added one at a time to a growing DNA chain attached to a solid support, using cycles of deprotection, coupling, capping, and oxidation.
• This method is highly automated and used commercially.
• Citation: PMC article on oligo synthesis

2. Why oligos >200 nt are difficult

• Error accumulation: Each added nucleotide can fail, and errors compound with longer chains.
• Practical limit: High-purity oligos become impossible above ~200 nt.
• Chemical constraints: Steric hindrance and protecting group limitations reduce efficiency.

3. Why a 2000 bp gene cannot be synthesized directly

• 2000 bp is far beyond the ~200 nt limit of direct chemical synthesis.
• Long genes are instead assembled from short oligos using methods like PCR assembly or Gibson assembly.
• Direct synthesis of a 2 kb gene would yield mostly truncated or error-prone products.

George Church

Option Chosen: 10 essential amino acids and Lysine Contingency

• Essential amino acids in most animals: histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine.
• (Arginine can be conditionally essential in children or certain species.)

Lysine Contingency:

• Fictional mechanism in Jurassic Park where engineered organisms cannot make lysine and therefore depend on an external supply.
• In reality, lysine is already essential, but organisms can survive in nature because lysine is widely available in food.
• This highlights that engineered dependencies could theoretically control survival, but natural environmental availability must be considered.

Citation:

• Wikipedia: Essential amino acid
• Jurassic Park Lysine Contingency

Week 1 Lab: Pipetting

Individual Final Project

Group Final Project