How to use: Set up your camera facing a whiteboard, flip chart, or even a big window (draw on it with dry-erase markers — it wipes off). Hit record. Pick a pathway. Draw and explain it from memory. No notes. No pausing. Just you, the marker, and the pathway.
Why video specifically: Watching yourself draw and explain is a DIFFERENT learning experience from listening to audio. You see your own hesitations. You see where your diagram breaks down. You see the spatial relationships between molecules. And when you review the video, the visual-spatial encoding from the drawing PLUS your own voice PLUS seeing your own body creates a uniquely powerful multi-modal memory trace.
The rule: You are NOT allowed to look anything up while recording. Draw what you remember. When you get stuck, say "I think it goes here but I'm not sure" and keep going. The gaps you discover on camera are your revision priorities.
Each session is 10-15 minutes:
- State the pathway (30 sec) — "Today I'm drawing the TLR-4 to NF-kB pathway from memory."
- Draw and narrate (8-12 min) — Draw each step, explain it as you go, make connections
- Self-assessment (2 min) — Step back, look at the whole thing, grade yourself. What did you miss? What was shaky?
Start with: Draw a macrophage (big circle). Draw TLR-4 on its surface. Draw LPS approaching.
Build outward:
- LPS binds TLR-4 (with help from MD2 and CD14 — bonus marks if you remember these)
- Intracellular: MyD88 adapter recruitment
- MyD88 → IRAK-1/IRAK-4 (phosphorylation)
- IRAK → TRAF6
- TRAF6 → IKK complex (IKK-alpha, IKK-beta, NEMO)
- IKK phosphorylates I-kappa-B (the inhibitor)
- I-kappa-B ubiquitinated → proteasomal degradation
- NF-kappa-B (p50/p65 dimer) freed → translocates to nucleus
- Binds kB response elements on DNA
- Gene transcription: TNF-alpha, IL-1-beta, IL-6, COX-2, iNOS
Then extend: Draw arrows from each cytokine showing what it DOES:
- TNF-alpha → endothelium (selectin expression, neutrophil recruitment)
- IL-1-beta → hypothalamus (fever via PGE2)
- IL-6 → liver (CRP, acute phase proteins)
- COX-2 → arachidonic acid → PGE2 (pain, fever, vasodilation)
Challenge mode: Now draw the RESOLUTION side on the other half of the board:
- Eicosanoid class switch: same arachidonic acid → 15-LOX → Lipoxin A4
- EPA → Resolvin E series
- DHA → Resolvin D series, Protectin D1, Maresins
- Connect resolution mediators to: stop neutrophil recruitment, M1→M2 switch, efferocytosis
When you're done: You should have the entire inflammatory arc — initiation to resolution — on one board. Step back. Film yourself pointing at the whole thing and summarising in 60 seconds.
Start with: Draw the brain (rough outline). Mark the hypothalamus, the anterior pituitary below it, and the adrenal glands at the bottom.
Build the cascade:
- Stress input → amygdala → paraventricular nucleus of hypothalamus
- PVN releases CRH into hypophyseal portal system (draw the portal vessels!)
- CRH → anterior pituitary → corticotrophs → POMC cleavage → ACTH
- ACTH → systemic circulation → adrenal cortex (zona fasciculata)
- Zona fasciculata: cholesterol → pregnenolone → progesterone → 11-deoxycortisol → CORTISOL
- Draw cortisol entering bloodstream
Add cortisol's targets:
- Liver: gluconeogenesis, glycogenolysis → glucose mobilisation
- Adipose: lipolysis → fatty acid mobilisation
- Muscle: protein catabolism (amino acids for gluconeogenesis)
- Immune system: immunosuppression (acutely)
- Brain: enhanced vigilance, altered memory encoding
Draw the negative feedback loop:
- Cortisol → hippocampus (GR receptors) → reduces CRH release
- Cortisol → hypothalamus (GR receptors) → reduces CRH release
- Cortisol → anterior pituitary → reduces ACTH release
- THIS LOOP IS THE OFF-SWITCH
Now draw what goes WRONG chronically:
- Use a different colour marker
- Chronic cortisol → hippocampal dendritic retraction → impaired feedback → loop breaks
- Chronic cortisol → immune cell GR downregulation → glucocorticoid resistance
- Loss of diurnal rhythm (draw a flat line vs the normal wave)
Start with: Draw a muscle cell. Draw an insulin receptor (tyrosine kinase) on the surface. Draw insulin approaching.
The normal relay:
- Insulin binds → receptor auto-phosphorylation (tyrosine)
- IRS-1 recruited and tyrosine-phosphorylated
- IRS-1 → PI3K activation
- PI3K: PIP2 → PIP3
- PIP3 → Akt (PKB) recruitment and phosphorylation
- Akt → AS160 phosphorylation
- AS160 releases brake on GLUT4 vesicles
- GLUT4 translocates to cell surface → glucose enters
Now draw the sabotage (different colour):
- TNF-alpha from inflamed adipose tissue
- TNF-alpha → SERINE phosphorylation of IRS-1 (NOT tyrosine)
- Serine-phosphorylated IRS-1 can't propagate the signal
- PI3K never activates → Akt stays off → GLUT4 stays inside
- Glucose locked OUT = insulin resistance
Add the AMPK back door:
- Exercise → ATP↓ AMP↑ → AMPK activates
- AMPK → GLUT4 translocation (INDEPENDENT of insulin pathway)
- Draw this as a separate arrow bypassing the entire broken relay
- Label it: "Why exercise helps insulin resistance even when the signalling is broken"
Start with: Draw tryptophan at the top centre.
The normal path (one side):
- Tryptophan → tryptophan hydroxylase → 5-HTP → AADC → serotonin
- Serotonin → AANAT → N-acetylserotonin → HIOMT → melatonin
- Label: mood, sleep, circadian rhythm
The immune diversion (other side):
- Inflammation → IFN-gamma, TNF-alpha → IDO enzyme induction
- Tryptophan → IDO → kynurenine (draw a big arrow stealing tryptophan away from serotonin)
- Kynurenine branches:
- → kynurenic acid (KYNA) — NMDA antagonist, neuroprotective but cognitive dulling
- → 3-hydroxykynurenine → 3-HAA → quinolinic acid (QUIN) — NMDA agonist, EXCITOTOXIC, neurotoxic
- Draw QUIN in red. This is the danger molecule.
- Label: neurodegeneration, depression, cognitive impairment
The clinical implication:
- Draw an SSRI acting at the synapse — recycling serotonin
- But if tryptophan was diverted upstream, there's less serotonin TO recycle
- Arrow back to: fix the INFLAMMATION to restore tryptophan allocation
- This is why "treatment-resistant depression" may be an inflammatory condition
Start with: Draw a cross-section of the gut wall — lumen at top, lamina propria below.
The barrier:
- Epithelial cells in a row (single layer!)
- Tight junctions between them (label claudins, occludin, ZO-1)
- Mucus layer above the epithelium (inner dense layer, outer loose layer)
- Zonulin as a gate controller
The lumen side:
- Commensal bacteria: Lactobacillus, Bifidobacterium, F. prausnitzii, Akkermansia
- Label Akkermansia in the mucus layer (it EATS mucin and stimulates mucus renewal)
- Pathobionts: gram-negative bacteria releasing LPS
- Food antigens, gliadin
The immune layer below:
- Macrophages patrolling the lamina propria
- Dendritic cells extending dendrites BETWEEN epithelial cells (sampling without breaking the barrier)
- Peyer's patches (draw a cluster) with M cells that sample and transport antigens
- IgA being secreted into the lumen (transcytosis)
- Draw the vagus nerve running along the side (afferent signals to brain)
The breach scenario:
- Gliadin → zonulin release → tight junctions open
- LPS crosses into lamina propria
- Macrophage TLR-4 binds LPS → NF-kB → cytokines
- Cytokines enter bloodstream → systemic inflammation
- Signal travels via vagus to brain → sickness behaviour
The repair protocol (different colour):
- Glutamine → enterocyte fuel
- Zinc → tight junction assembly
- Butyrate (from fibre fermentation) → enterocyte fuel + Treg induction
- Omega-3 → SPMs for mucosal resolution
- Probiotics → restore commensal dominance
Start with: Draw three kingdoms: BRAIN, IMMUNE SYSTEM, MUSCLE/METABOLISM. Draw a central treasury labelled "~2000 kcal/day GLUCOSE"
Peacetime allocation:
- Brain: 400 kcal (20% of total — draw this disproportionately large)
- Muscle/movement: variable, dependent on activity
- Immune surveillance: modest, background patrol
- Gut, liver, kidneys: their cuts
Wartime (immune activation):
- Immune system requisitions up to 30% additional
- Draw arrows stealing from muscle and liver
- TNF-alpha → insulin resistance in muscle (glucose diverted to immune cells)
- Immune cells use Warburg metabolism (glycolysis, even with oxygen available — speed over efficiency)
- Brain activates HPA axis → cortisol → mobilise more glucose from liver
- Draw sickness behaviour: fatigue, anorexia, social withdrawal (energy conservation)
The chronic stalemate:
- Immune system never resolves → keeps demanding glucose
- Brain cortisol stays high → glucocorticoid resistance → can't suppress immune
- Muscle wastes (sarcopenia) — amino acids raided for gluconeogenesis
- Fat stores mobilised but also INFLAMED (draw M1 macrophages in adipose tissue)
- Draw a feedback loop: inflamed fat → more TNF-alpha → more insulin resistance → more inflammation
Start with: Draw a 24-hour clock face. Mark dawn, noon, dusk, midnight.
Cortisol rhythm:
- Peak: 30-45 min after waking (cortisol awakening response)
- Gradual decline through the day
- Nadir: around midnight
- Draw the wave
Melatonin rhythm (mirror image):
- Onset: ~2 hours after darkness (dim light melatonin onset — DLMO)
- Peak: 2-4am
- Decline: before dawn
- Draw the inverse wave
Immune oscillation across 24h:
- Daytime: cortisol dominant → immune cells in circulation, acute response capacity high
- Nighttime: melatonin dominant → T-cells traffic to lymph nodes, adaptive immune learning
- NK cell activity: peaks during sleep
- Pro-inflammatory cytokine production: increases at night (TNF-alpha, IL-1 — this is why fevers spike at night)
- Growth hormone: pulses during slow-wave sleep → tissue repair
Clock genes in immune cells:
- Draw inside a macrophage: BMAL1/CLOCK → PER/CRY → feedback loop
- TLR4 expression oscillates with circadian rhythm
- NF-kB activity has circadian gating
- Macrophage phagocytic capacity varies by time of day
The disruption scenario:
- Blue light at night → melanopsin → SCN says "daytime" → pineal suppresses melatonin
- Draw the wave flattening
- Consequences: reduced NK activity, impaired T-cell trafficking, loss of antioxidant flush, reduced autophagy, elevated evening cortisol
After each whiteboard session:
- Watch the video the next day — notice where you hesitated, drew wrong, or skipped steps
- Make a "corrections" video — film yourself correcting the board with a different colour marker
- Speed challenge — try the same pathway one week later, time yourself. Can you do it in half the time?
- Peer teaching — invite a classmate over and draw the pathway for them. If THEY can follow it, you know it.
- Screenshot and annotate — pause the video at the finished board, screenshot it, import to Obsidian as a visual reference
- A whiteboard, flip chart, or large window (dry-erase markers wipe off glass)
- 3-4 colours of dry-erase marker (black for structure, red for pathology, green for resolution/repair, blue for connections)
- Phone or camera on a tripod facing the board
- That's it. No editing. No production. Raw and messy is the point.
| Session |
Pathway |
Attempted |
Reviewed |
Corrected |
Taught to someone |
| 1 |
TLR-4 → NF-kB → Resolution |
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| 2 |
HPA Axis |
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| 3 |
Insulin Signalling |
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| 4 |
Kynurenine Pathway |
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| 5 |
Gut Barrier |
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| 6 |
Selfish Systems |
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| 7 |
Circadian Immune Rhythm |
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