Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
Craniofacial Research Track
Session 14The Fix, January (intensive)Lens: Genetics of Disease
CRISPR-Cas9: programmable molecular scissors
Discovery question
We know the gene change behind Mateo's . If we could rewrite one short stretch of DNA, what tool would let us find that exact spot and change it?
is programmable: a short guide RNA is written to match a chosen DNA site, the Cas9 cuts there, and the cell's repair can be steered to change the sequence back toward the healthy version.
The plan
Prerequisite check
Before this page, you should know
- ClinVar is a public archive of reported genetic variants and what they mean for health.
- A is classified as disease-causing; a has an unknown effect.
If not, review
Today's new idea is only
is programmable: a short guide RNA is written to match a chosen DNA site, the Cas9 cuts there, and the cell's repair can be steered to change the sequence back toward the healthy version.
Learn first
What to learn
Goal: Explain how a guide RNA targets a DNA site, how Cas9 cuts, and how a cut can lead to gene correction.
Know by the end
- A guide RNA is a short RNA written to match a chosen target by base pairing.
- Cas9 is the that does the cutting; the guide RNA steers it to the right spot.
- Cas9 makes a cut in the DNA, and the cell then repairs that cut.
- If a healthy template is supplied during repair, the cell can copy it and the sequence is changed back toward the healthy version (gene correction).
- is programmable: change the guide RNA and you change the target, without changing the Cas9 .
The plan
Guided notes
1
The three parts
Model start: The guide RNA is a short RNA whose letters match the target DNA, so it finds and binds the one spot we chose.
- Label a simple diagram with the three parts: the target DNA, the guide RNA, and the Cas9 .
- In one sentence each, write the job of the guide RNA and the job of Cas9.
2
Find, cut, repair
Model start: First the guide RNA binds the matching DNA site, then Cas9 cuts at that spot, then the cell repairs the cut.
- Put these steps in order: Cas9 cuts the DNA, the guide RNA binds the matching site, the cell repairs the cut.
- Explain why we say is programmable, using the words guide RNA and target.
3
From a cut to a correction
Model start: Gene correction means repairing a disease-causing DNA change back toward the healthy sequence; here that is the IRF6 change behind Mateo's .
- A cut by itself is not a fix. Explain what has to be supplied so the cell repairs toward the healthy sequence.
- Connect this to Mateo: which gene change from Phase 3 would a correction aim to repair?
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Peer-reviewed literature on IRF6 in clefting (PubMed)
Why this source matters
This is the published evidence behind today's idea: is programmable: a short guide RNA is written to match a chosen DNA site, the Cas9 cuts there, and the cell's repair can be steered to change the sequence back toward the healthy version.
Words to unlock first
Reading moves
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Stop point
You do not need the methods or statistics yet. If a sentence is about lab technique or math you have not learned, mark it and skip it.
Your output
Write one claim-evidence sentence: what this source claims, and the one piece of evidence that backs it up.
Lab day
Using the database (what to capture)
MedlinePlus
Open the tool Plain-language explanations of a gene or condition, written for patients and families.
When you use this: Use this when a research paper is too dense, or when you need to explain a finding to Mateo's family in everyday words.
What the screen looks like
Step by step
- 1Open medlineplus.gov/genetics and search the gene or condition (IRF6).
- 2Read the summary written in everyday words.
- 3Note the conditions the gene is linked to at the bottom of the page.
Capture these fields
- Topic: IRF6 gene
- Plain-language summary: IRF6 helps the tissues of the face join correctly before birth.
- Linked conditions: Van der Woude syndrome; nonsyndromic cleft
How to read it: Start here when a research paper is too dense. MedlinePlus gives you the gist in everyday words so you can go back to the harder source knowing what it is about.
Lost? About MedlinePlus GeneticsLearn first
Pick your level
Level 1, Guided
Use the sentence starters, a word bank from the vocabulary, a labeled diagram, and the exact source link.
Level 2, Collaborative
Complete a partly blank model or table and explain it.
Level 3, Independent
Make a claim from a new example or an unfamiliar entry in the same database.
The plan
Work as a research team
Team roles
- Manager: keeps the group moving
- Recorder: writes the shared model or table
- Evidence checker: verifies each claim against the source
- Reporter: explains the group's reasoning
Process reflection
- What evidence changed your thinking today?
- What did your group disagree about, and how did you resolve it?
- What question is still unresolved?
Check yourself
Demonstration of learning
By the end of this session, submit ONE of: a labeled diagram with a 2-sentence explanation; a claim, evidence, reasoning paragraph; a completed data table from a real database; or a one-question exit ticket using today's vocabulary.
Meets standard if your explanation correctly connects structure, timing, gene or protein function, or evidence source to Mateo's case: Explain how a guide RNA targets a DNA site, how Cas9 cuts, and how a cut can lead to gene correction.
How this is graded (rubric)
For: Explain how a guide RNA targets a DNA site, how Cas9 cuts, and how a cut can lead to gene correction.
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in the right way (Schoology for routine work) and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
How the model answer scores against this rubric
- CompleteProficient: Nothing is left blank: the model fills every part of "Explain how a guide RNA targets a DNA site, how Cas9 cuts, and how a cut can lead to gene correction.".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be turned in on Schoology and confirmed.