CURRENT FOCUS
What if skin type is the wrong question?
Geraint Thomas Bio follows questions like these through the biology underneath them. Right now, the focus is epidermal biology and the science behind skincare, with new topics added as the work develops.
evidence in context
What can a cell study really tell us?
barrier signalling
How does skin detect damage?
measurement
What does TEWL actually measure?
Latest
Ways into the science
01 / Foundations
Scratch the surface.
Start with the core biology behind the subject.
02 / Mechanisms
Under the skin.
See how cells, signals, lipids and environmental inputs interact.
03 / Deep dives
Down the rabbit hole.
Take one question through the evidence and the competing explanations.
The Damaged Skin Barrier
The long-form version of the questions that started this site.
Written for scientifically curious readers and skin professionals.
01 / STRUCTURE
What is it made of?
Corneocytes, organised lipids and the adhesive structures that hold the sheet together.
02 / REGULATION
How is it regulated?
Surface pH, enzyme activity and a calcium gradient coordinate renewal.
03 / PRESSURE
What pushes it out of balance?
Cleansing, actives, friction, UV and hard water, accumulating on one tissue.
04 / RECOVERY
What does recovery involve?
Feeling better can arrive before the structure is rebuilt.
The skin, by scale.
Six depths, from the whole organ to a single molecule. Select one to zoom in.
Zoomed in · illustrative, not to scale
01 · The organ
The body's boundary.
Roughly 1.5 to 2 m² of surface
Around two square metres of tissue deciding, continuously, what gets in and what stays. Most of that decision is made in the outermost fraction of a millimetre.
02 · The epidermis
Rebuilt from the bottom up.
About 0.1 mm over most of the body
Roughly the thickness of a sheet of paper. New cells form at the base and take around six weeks to reach the surface, changing all the way up.
03 · The stratum corneum
Dead, and still working.
15 to 20 cell layers, 10 to 20 µm
The outermost layers are no longer alive in the cellular sense. They still hold water in, keep most things out and shed on a controlled schedule.
04 · The corneocyte
The brick.
30 to 40 µm across, under 1 µm thick
A flattened cell packed with keratin and sealed inside a cornified envelope. Wide and extraordinarily thin, tiled against its neighbours.
05 · The lipid matrix
The mortar.
Lamellae repeating at roughly 13 nm
Ceramides, cholesterol and free fatty acids stacked in ordered sheets between the corneocytes. Their organisation sets how quickly water escapes.
06 · The molecule
Where the barrier is decided.
A few nanometres
Filaggrin, ceramides and the enzymes that process them. Most of what happens at the surface was settled here, long before it arrived.
Scale figures are approximate adult values. Images are illustrations.
Trace the claim.
Every claim should have a paper trail.
Pick a claim and pull on it. Each underlined phrase hides a question about what was actually done.
A result is only as strong as the experiment behind it.
.
Select an underlined phrase.Loss how?
Inherited loss-of-function variants, seen in large genetic studies and reproduced in animal models.
Lower filaggrin in inflamed skin. Inflammation itself switches filaggrin down, so this can't tell cause from effect.
What exactly was measured?
Genotype and protein level, measured separately. The gene's long repeats make it hard to sequence.
One antibody stain on a biopsy.
Cause, or just correlated?
Present from birth, effect rising with the number of faulty copies, and replicated in independent cohorts.
Skin samples compared at a single point in time.
For whom, and how much of it?
An effect size, including the carriers who never develop it.
"Causes", with no word on how many people it fails to explain.
to .
Select an underlined phrase.Is it selective, and is it the target?
A dose-response curve, plus a genetic knockdown of the target that gives the same result.
One compound at one dose. Many inhibitors hit more than their named target.
More than the sum of the parts?
A formal synergy analysis across a range of doses.
The combination kills more than either alone, read as synergy. Two additive effects look identical.
Which cells?
Several cell lines, ideally primary cells, with healthy cells as a safety check.
One cell line, grown in a dish for years.
Death, or a drop in a readout?
Caspase cleavage or annexin V staining, which show apoptosis directly.
A viability dye, which measures metabolic activity and not death.
of protein X .
Select an underlined phrase.Where was the line drawn?
A threshold set before looking at outcomes, or tested in a second cohort.
The cut-off that gave the best result in the same data.
Expression of what, and where?
Protein measured in the relevant cell type, with mRNA as support.
Bulk mRNA from a sample that mixes tumour with everything around it.
Predicts, or just tracks?
Holds after adjusting for stage and age, and in a separate cohort.
A correlation in one dataset. Stage alone might explain it.
Worse by what measure?
A defined endpoint such as overall survival, with enough events and follow-up to trust it.
A vague "prognosis" from few patients and a short follow-up.
How many, and how independent?
Biological replicates are separate experiments or people. Technical replicates are the same sample measured again. Three wells is not an n of three.
Who measured, and did they know the answer?
Blinding matters most where the readout involves judgement, like scoring a stain or grading a lesion.
Has anyone else got the same result?
One lab with one method is a lead. A different lab with a different method is evidence.
Hello, I'm Geraint.
I’m a biochemist interested in how biological systems behave, adapt, and more so, when and why they fail.
I took an integrated master’s in biochemistry at Cardiff University and graduated with a First. My research year was at the European Cancer Stem Cell Research Institute, studying how breast cancer stem-like cells resist death-receptor signalling.
After that I spent several years outside science. Skin biology is what brought me back.
The way of thinking carried over: what was measured, in what, and what does the mechanism say? The epidermis turned out to be a good place to use it. It became The Damaged Skin Barrier and this site. I wrote the book, drew its figures and built the platform myself.
Where next?
Read, check a source, or meet the person behind it. Every route leads back to the evidence.