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L02 — Broken Code

Module: M06 — Rewriting Life
Periods: 1
NGSS: HS-LS1-1, HS-LS3-2
Lesson Type: Explore / Explain

Learning Objective

  • By the end of this lesson, students will be able to analyze how a single-base mutation in a gene can alter protein structure and cause disease by tracing the sickle cell mutation from DNA → mRNA → amino acid → protein shape.

Phenomenon / Hook

Display two images side by side: normal round red blood cells vs. sickle-shaped cells (search Wikimedia Commons: “sickle cell blood smear”). Optional: show opening of Can CRISPR cure Sickle-cell Disease? (0:00–1:00) for real-patient context. “One letter change — out of 3 billion — turns round cells into rigid crescents that block blood vessels. How does a single ‘typo’ in DNA cause a disease that affects millions?”

Materials

  • Handout: [[resources/handouts/sickle-cell-tracing-sheet]] (DNA → mRNA → amino acid → protein shape)
  • Amino acid codon chart (student reference)
  • Pipe cleaners or modeling clay (for protein folding)
  • Projector for side-by-side cell images

Agenda

Opening (5 min)

  • Show normal vs. sickle cells image
  • Quick write: “What could cause a red blood cell to change shape?”
  • Share 2–3 responses; bridge to DNA

Explore (18 min)

  • Sickle Cell Tracing Activity (Pairs)
    • Students receive the DNA sequence of the HBB gene (β-globin)
    • They transcribe → mRNA → translate using codon chart
    • They identify the single-base mutation (GAG → GTG → valine instead of glutamic acid)
    • Key questions:
      1. Which base changed? (6th codon, A → T)
      2. Which amino acid changed? (glutamic acid → valine)
      3. Why does one amino acid change matter? (hydrophobic valine causes hemoglobin to clump)
    • Extension: Use pipe cleaners to model how a hydrophilic → hydrophobic substitution changes folding

Explain (12 min)

  • Teacher-led discussion connecting mutation → protein shape → cell shape → disease
    • Chain of causation: DNA base change → different amino acid → altered protein folding → hemoglobin polymerizes → cell sickles → blocks vessels → pain, organ damage
  • Introduce vocabulary: point mutation, missense mutation, genotype, phenotype
  • Address the question: “Could CRISPR fix this?” — Bridge to L03

Elaborate (5 min)

  • Students complete a quick comparison table:
FeatureNormal HemoglobinSickle Hemoglobin
DNA codonGAGGTG
Amino acidGlutamic acidValine
Protein shapeNormal foldingClumps/polymerizes
Cell shapeRound, flexibleRigid crescent
Health effectNormal blood flowBlocked vessels, pain

Closing (5 min)

  • Exit Ticket: [[exit-tickets/L02-exit-ticket]]
    1. How does a single DNA base change lead to sickle cell disease? Trace the steps.
    2. If you could use CRISPR to fix this mutation, what would you change in the DNA?

Differentiation

SupportExtension
Provide a partially completed tracing sheet with the first two steps doneChallenge: Why might having ONE copy of the sickle allele be advantageous in malaria regions? (heterozygote advantage — preview of evolution, M07)
Pair struggling students with stronger partnersResearch: Are there other diseases caused by single-base mutations? (CF, PKU, etc.)

Assessment

  • Formative: Check tracing sheets during activity; look for correct transcription and translation
  • Exit Ticket: Chain-of-causation reasoning

Teacher Notes

  • The codon chart is essential — have extras printed.
  • Students often confuse DNA base substitution with amino acid substitution. Reinforce: the codon chart is the bridge.
  • The pipe cleaner protein folding is optional but highly engaging for tactile learners. Prep clay or pipe cleaners in advance.
  • If time is short, the comparison table can become homework.