Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.

The five-domain case curriculum

The Baby Mateo Case

One patient, five specialist teams, one answer that students discover for themselves.

The case

Baby Mateo

A composite patient (no real data) born at term with a complete unilateral (left) cleft lip and palate, no other birth defects.

Interactive infographics

Explore the case as interactive infographics

A companion web app turns the five-domain lesson progressions into interactive infographics: each domain's 20-step pathway with its takeaways, skills, vocabulary, and the connector to the next decision point, plus the overall five-team convergence map.

Open the infographic suite

Opens the live app in a new tab.

Learn first

Five teams, one patient

Five specialist teams investigate the same one patient, one team per course. Each team runs Mateo's case for twenty discovery lessons through its own lens, and the teams converge on one shared picture of the same child.

Each domain owns one course: Developmental (PBS), Genetics (Medical Interventions), Anatomical (HBS), and Experimental Design (BI), with the Disease domain as the shared clinical backbone that the other four plug into.

DevelopmentalPrinciples of Biomedical Science (PBS)GeneticsMedical Interventions (MI), with PBS overlap AnatomicalHuman Body Systems (HBS)Experimental DesignBiomedical Innovations (BI)DiseaseShared clinical backbone (the cleft team)

Discovery learning

Students are never told what Mateo has. Each lesson drops a breadcrumb the next one builds on, so students reason their own way to the answer. The diagnosis is the destination every team reaches at its Lesson 20 synthesis, discovered, not declared.

Developmental domain

Principles of Biomedical Science (PBS)

Team lead: Lead Developmental Biologist

Normal lip and palate fusion and the cranial neural crest, normal versus failed, from cell to structure.

Teacher-only domain report Teacher-only lesson map Teacher-only lessons (zip)

#	Lesson	Learning goal
1	When could Mateo's cleft have happened?	Place craniofacial development on a week-by-week timeline (weeks 4 to 12) and find the window a cleft must originate in.
2	Which building blocks must fuse to make a lip and palate?	Name and locate the five facial prominences and which must fuse to build a normal upper lip.
3	Where do the cells that build the face come from?	Describe the origin of cranial neural crest cells at the neural folds, delamination by EMT, and why they are multipotent.
4	How do the face-building cells get to the right place?	Describe how cranial neural crest cells migrate in streams into the prominences and pharyngeal arches.
5	How and when does the upper lip close?	Explain that the upper lip closes when the nasal and maxillary prominences fuse at weeks 6 to 7, the step that fails in a cleft lip.
6	How the palate begins (shelf outgrowth)	Explain that the secondary palate begins as two shelves growing downward, driven by signal-driven proliferation.
7	Getting above the tongue (shelf elevation)	Explain how vertical palatal shelves rotate to horizontal above the tongue, and a cause of failed elevation.
8	Two shelves become one roof (adhesion and the seam)	Describe how shelves adhere at the medial edge epithelium and form a single midline seam.
9	What happens to the wall between the shelves (seam removal)	Explain why the midline seam must be removed and compare the candidate mechanisms (EMT, apoptosis, extrusion).
10	What tells tissues when and where to grow (SHH, BMP, FGF)	Explain that SHH, BMP, and FGF signaling centers schedule growth, and losing a signal mis-grows a shelf.
11	TGF-beta3, the fusion switch in the medial edge epithelium	Explain that TGF-beta3 is required for shelves to stick and dissolve the seam, and predict the cleft when it is missing.
12	The Wnt/beta-catenin master switch	Explain that Wnt/beta-catenin tells a cranial cell to become bone or skin by repressing the default cartilage program.
13	Periderm and IRF6, the non-stick coating on the embryo	Explain that periderm made by IRF6 keeps oral surfaces from sticking to the wrong neighbors and blocking fusion.
14	Mapping the failure (cleft lip versus cleft palate)	Map a cleft phenotype back to the exact developmental step that failed and distinguish a local from a broad defect.
15	Critical timing windows, when the door closes	Explain that each fusion step has a narrow critical window, and once it closes the cleft cannot be undone.
16	When the outside world reaches the embryo	Explain how folate, smoking, and valproate change the odds of fusion, as risk-modifiers rather than single causes.
17	Same DNA, different outcome	Describe how DNA methylation and microRNAs change gene activity, and use the second-hit idea to explain difference.
18	Watching development happen	Explain why scientists use model organisms and live imaging, and judge what each tool can and cannot show.
19	If we know the window and the signal, could we prevent a cleft?	Use real mouse rescue experiments to explain rescue logic and judge honestly why it is preclinical.
20	Mateo's complete developmental story	Assemble the evidence into one normal-versus-failed account: an isolated failure of fusion in a specific window.

Students name Mateo's diagnosis only at Lesson 20, reasoning to it from the evidence rather than being told it.

Genetics domain

Medical Interventions (MI), with PBS overlap

Team lead: Head Medical Geneticist

IRF6, from inception to treatment: from is-it-even-genetic down to the gene, its variants, proof, risk, and the treatment horizon.

Teacher-only domain report Teacher-only lesson map Teacher-only lessons (zip)

#	Lesson	Learning goal
1	Chance or genetic? Reading Mateo's family tree	Read and build a three-generation pedigree, and tell an isolated cleft from a familial one when history is sparse.
2	Screening for a hidden syndrome	Triage a cleft by associated features, learn the Van der Woude lip-pit flag, and decide Mateo's cleft looks nonsyndromic.
3	Does it run in families like a single gene?	Compare clean autosomal dominant inheritance against the multifactorial threshold model for Mateo's sparse pedigree.
4	Hunting the exemplar cleft gene: linkage to 1q32	Use linkage and co-segregation in informative families to narrow the exemplar cleft gene to a chromosomal region (1q32).
5	The gene at 1q32 has a name: IRF6, from DNA to protein	Trace a gene from DNA to mRNA to protein and identify IRF6 as the exemplar cleft gene.
6	Looking up a variant	Navigate ClinVar and OMIM and classify a variant as benign, pathogenic, or of uncertain significance.
7	Kinds of typos in DNA	Classify a DNA change as missense, nonsense, frameshift, or splice from a sequence and predict its effect.
8	One gene, two diseases	Connect mutation mechanism to phenotype: haploinsufficiency (milder VWS) versus dominant-negative (more severe PPS).
9	The hidden regulatory variant	Distinguish coding from regulatory variants and explain how rs642961 raises risk by disrupting an AP-2alpha enhancer.
10	What the IRF6 protein looks like	Describe IRF6's two-domain architecture (DNA-binding and protein-binding) and why domain location predicts effect.
11	Is this gene important across species?	Use BLAST alignment and sequence conservation as evidence of functional importance.
12	How does one wrong amino acid break the protein?	Connect protein structure to function using AlphaFold and predict how a single missense disrupts folding or binding.
13	Does IRF6 work alone?	Read a gene regulatory network and place IRF6 in the p63 to IRF6 to GRHL3 axis.
14	What does IRF6 actually do in the embryo?	Connect IRF6 to a cell behavior: IRF6 makes periderm cells differentiate so palatal shelves can fuse.
15	How do we prove the gene causes it?	Use knockout and rescue logic in mouse and zebrafish to argue causation, not correlation.
16	Why is CL/P more common in some groups?	Explain how allele frequency, ancestry, gene-environment, and a liability threshold combine across populations.
17	What is the family's recurrence risk?	Apply Mendelian and multifactorial empiric recurrence-risk figures and describe the counselor's ethical role.
18	Can we fix the code?	Describe three molecular strategies (CRISPR correction, gene-dosage, protein or mRNA rescue) and that each is preclinical.
19	Should we, and who decides?	Weigh somatic versus germline editing and prenatal intervention against benefit, risk, equity, and consent.
20	What is Mateo's complete genetic story?	Assemble the workup into a Domain Report linking clue, gene, variant, protein, network, proof, risk, treatment, and ethics.

Students name Mateo's diagnosis only at Lesson 20, reasoning to it from the evidence rather than being told it.

Anatomical domain

Human Body Systems (HBS)

Team lead: Lead Craniofacial Surgeon

Form to repair to consequence: normal anatomy, cleft anatomy, the staged surgical rebuild, and what even a good repair leaves behind.

Teacher-only domain report Teacher-only lesson map Teacher-only lessons (zip)

#	Lesson	Learning goal
1	The normal lip and palate, part by part	Label the normal lip, palate, and nasal floor and explain that the palate is a wall separating mouth from nose.
2	The muscles that make a lip and palate work	Describe the orbicularis oris ring and the levator veli palatini sling and why muscle fiber direction matters.
3	The anatomy of the cleft, what is actually interrupted	Explain that a cleft is a gap where tissue failed to join and the muscles insert wrong and pull the wrong way.
4	Saying it precisely, how surgeons classify a cleft	Use the Veau, LAHSHAL, and Kernahan systems and place Mateo as a complete unilateral left cleft (Veau III).
5	One cleft, many shapes, the cleft spectrum	Distinguish clefts along three axes (unilateral/bilateral, complete/incomplete, overt/submucous) and place Mateo.
6	Why feeding fails, and what helps right now	Explain why an open cleft prevents suction and recommend the feeding interventions that compensate.
7	Shaping the gap before surgery	Explain how nasoalveolar molding narrows the gap and improves nasal symmetry, and weigh the evidence.
8	Rebuilding the lip	Explain that lip repair reconstructs the orbicularis oris ring, and compare three named techniques.
9	Rebuilding the roof of the mouth	Explain that palatoplasty must close the oronasal hole AND reconstruct the levator sling, comparing named techniques.
10	When to repair, and why the calendar matters	Explain why lip repair is at about 3 months and palate at 9 to 12 months, balancing safety, growth, and speech.
11	How palate repair lets a child speak	Explain the velopharyngeal valve and why a repaired sling decides between clear speech and VPI.
12	Why cleft children get so many ear infections	Trace how abnormal palate muscles fail to open the Eustachian tube, causing middle-ear fluid and hearing risk.
13	The cleft runs through the teeth	Explain why a cleft through the alveolus disrupts the dentition and how cleft extent predicts hypodontia.
14	Filling the bony gap in the gum ridge	Explain why, when, and how an alveolar bone graft fills the cleft, and defend grafting before age 9 with data.
15	Why the repaired midface grows backward	Explain how a repaired cleft maxilla grows poorly forward, producing a flat midface and a Class III tendency.
16	Correcting the bite and the midface	Explain how orthodontics, Le Fort I advancement, and distraction correct a retruded cleft midface near maturity.
17	The cleft nose and its repair	Describe the cleft nasal deformity and explain why definitive rhinoplasty is timed to nasal growth.
18	When a repair falls short: fistula and VPI revision	Explain palatal fistula and VPI and compare pharyngeal flap versus sphincter pharyngoplasty as revisions.
19	Who does what, and when: Mateo's care timeline	Build a staged, age-ordered multidisciplinary care timeline for a child with complete unilateral CL/P.
20	Mateo's complete anatomical and surgical story	Synthesize one form-repair-consequence account and reason to an isolated, nonsyndromic complete unilateral CL/P (Veau III).

Students name Mateo's diagnosis only at Lesson 20, reasoning to it from the evidence rather than being told it.

Experimental Design domain

Biomedical Innovations (BI)

Team lead: Principal Investigator

One researchable question taken from inception to evidence, climbing the evidence hierarchy with real CL/P studies, ending in the student's own study.

Teacher-only domain report Teacher-only lesson map Teacher-only lessons (zip)

#	Lesson	Learning goal
1	From an observation to a researchable question	Convert an observation about Mateo into a focused PICO question and separate researchable from non-researchable questions.
2	From a question to a testable hypothesis	Write a testable hypothesis and null, and identify the independent, dependent, and controlled variables and control group.
3	Why we trust some studies more than others	Rank study designs in the evidence hierarchy and justify the ranking by how much bias each design controls.
4	Studying a cause you cannot assign	Explain how a case-control study works backward from outcome to exposure, compute an odds ratio, and name recall bias.
5	Measuring inheritance over time and in twins	Explain cohort and twin designs and read what high heritability does and does not tell us about a single gene.
6	Finding a risk gene among millions of bases	Explain how GWAS scans the genome and how the transmission disequilibrium test uses parents as built-in controls.
7	Is the association real, or just chance?	Interpret an odds ratio, a p-value, and a 95% confidence interval and decide whether an association is significant.
8	Why gene studies use such tiny p-values	Explain why testing many hypotheses inflates false positives and apply a genome-wide significance correction.
9	Taking a gene to the bench	Describe how knockout, in situ hybridization, and immunohistochemistry each test a different part of a gene's job.
10	CRISPR as an experimental tool	Explain how CRISPR-Cas9 edits a chosen DNA site and the two checks that make a CRISPR experiment trustworthy.
11	When is a mouse a good stand-in for Mateo?	Judge a model by face and construct validity and apply the 3Rs and ARRIVE reporting to a proposed mouse study.
12	Knock it out, then put it back: proving a gene causes a defect	Explain why a knockout alone cannot prove causation and how a rescue completes the causal argument.
13	The fairest test: comparing two treatments in real children	Explain how randomization, blinding, and intention-to-treat make a two-treatment comparison fair.
14	The TOPS trial: testing the best time to repair a palate	Walk a real RCT from question to result and read its primary outcome to state what it proved and what it did not.
15	How do you measure something as fuzzy as speech?	Turn a fuzzy concept into a defined outcome measure and explain why patient-reported outcomes matter.
16	What could fool us into the wrong conclusion?	Identify bias and confounding in a real cleft study and name the design defenses (matching, randomization, blinding).
17	How do we combine many studies into one answer?	Explain how a systematic review pools studies using PRISMA and when studies are too different to combine.
18	What makes research on children ethical?	Explain IRB approval, parental consent, child assent, and equipoise, and apply them to a proposed cleft study.
19	How does the world check that a study is trustworthy?	Explain reproducibility, reporting standards (CONSORT, STROBE), and peer review, and spot what a weak paper left out.
20	What new question about Mateo would you investigate, and how?	Design an original, ethical, well-controlled study using the full design checklist, and state how scientists tell isolated from syndromic clefting.

Students name Mateo's diagnosis only at Lesson 20, reasoning to it from the evidence rather than being told it.

Disease domain

Shared clinical backbone (the cleft team)

Team lead: Cleft Team Coordinator / Pediatrician

The whole-patient journey from birth diagnosis through lifelong multidisciplinary care, including the reasoning that rules syndromes in or out.

Teacher-only domain report Teacher-only lesson map Teacher-only lessons (zip)

#	Lesson	Learning goal
1	Day one: recognizing and communicating a cleft at birth	Perform a structured newborn lip-and-palate exam and communicate the finding clearly without alarming language.
2	Describing the cleft: type, side, and how complete	Classify a cleft by structures involved, laterality, and completeness, and apply that vocabulary to Mateo.
3	Is the cleft a clue? The syndromic question	Explain isolated versus syndromic clefts and frame Mateo as a genuine open question.
4	The short list: ruling out the big cleft syndromes	Match four high-stakes cleft syndromes to their red flags and show Mateo trips none.
5	The exam and the test that sort syndromic from isolated	Describe the dysmorphology exam and chromosomal microarray and why testing is targeted.
6	Keeping Mateo fed and growing	Explain why an open palate prevents normal sucking and choose feeding interventions that let Mateo grow.
7	When a cleft is an airway emergency	Identify the Pierre Robin sequence triad and place Mateo on the airway-risk spectrum.
8	How common is Mateo's cleft, and in whom?	Read real epidemiology and describe how prevalence varies by type, sex, ancestry, and laterality.
9	What caused Mateo's cleft?	Explain multifactorial causation using real twin and risk-factor data without blaming a single cause.
10	The plan for the next 18 years	Order the major stages of cleft care from birth through adolescence and explain why each is timed when it is.
11	What the surgeries are actually for	Explain the clinical purpose and approximate timing of lip and palate repair from the family's point of view.
12	How a repaired palate lets Mateo talk	Explain velopharyngeal closure, why a cleft causes hypernasal speech and VPI, and what the SLP does about it.
13	Protecting Mateo's hearing	Explain why cleft palate causes recurrent middle-ear fluid and conductive hearing loss, and how the team monitors it.
14	Caring for Mateo's teeth and bite	Describe cleft-related dental anomalies and why dental and orthodontic care is staged across childhood.
15	Is Mateo growing well?	Explain cleft infants' risk for poor feeding and slow growth, and how growth charts keep the whole child on track.
16	Supporting Mateo and his family beyond the body	Identify psychosocial needs across childhood and name realistic supports, honest about where evidence is thin.
17	Does every child like Mateo get the same care?	Explain that access is unequal across geography, income, and population, and describe the global burden and barriers.
18	A repaired cleft is not a cured cleft	Identify the major long-term complications and explain which team member catches each.
19	How a team delivers care without gaps	Explain why cleft care is multidisciplinary, name the core specialties, and describe how coordination prevents gaps.
20	Mateo's complete clinical story (and his diagnosis)	Synthesize all twenty lessons to reach and justify the diagnosis: isolated nonsyndromic CL/P, multifactorial, managed for a lifetime.

Students name Mateo's diagnosis only at Lesson 20, reasoning to it from the evidence rather than being told it.

Explore

How it was built, and the infographics

The canonical case, the five domain arcs, and the discovery breadcrumb trail are documented in the curriculum spec. The six infographic prompts (one per domain plus an overall five-team convergence map) are the source for the interactive suite.

Teacher-only curriculum spec Teacher-only research library index Master article index Teacher-only infographic prompts

Every fact in the curriculum is tied to a real retrieved source; anything uncertain is flagged, and no citations or data were invented.