Superresolution imaging of laminin 332 to dissect mechanism and develop treatments for junctional epidermolysis bullosa

Brief plain language background

Junctional epidermolysis bullosa (JEB) is a rare, inherited condition in which minor friction causes painful blistering of skin and mucous membranes. In the eye, repeated breakdown of the corneal epithelium leads to chronic erosions, scarring, vascular growth and, ultimately, vision loss. From infancy, patients face daily wound care,

infection risk and relentless pain. Simple acts like blinking, washing or touching can trigger new lesions. Current management relies on dressings, antibiotics and lubricants that treat symptoms but do nothing to prevent blistering. For those with corneal involvement, even routine ophthalmic procedures carry high risk. The absence of a cure means JEB sufferers endure lifelong disability, social isolation and emotional distress. A deeper understanding of the molecular foundations of tissue fragility in the cornea is essential to break this cycle of injury and enable truly restorative therapies.

What problem/knowledge gap does it help address

Multiple teams are developing treatments for JEB, yet there is no cornea-specific platform that can robustly predict clinical efficacy. Corneal epithelial cells depend on a protein called laminin-332, and a part of this, made from the LAMB3 gene, is faulty (mutated) in most JEB cases. Existing models don’t provide enough detail of how the laminin protein functions to explain how different patient mutations affect this protein. Additionally, current approaches used to test new drugs cannot process many samples at a time. Advanced imaging techniques including super-resolution microscopy now offers the chance to study how laminin-332 organises, how the mutation in LAMB3 disrupts cell adhesion and whether or how therapeutics restore normal architecture at a scale not previously possible. We will create a dual-use platform: for imaging and understanding of the disease, which can be used in candidate drug screens, to allow rapid testing of interventions to treat this debilitating disease.

Aim of the project

To deepen knowledge of laminin-332 biology and determine the impact of JEB disease-causing mutations on its role in corneal health. It also seeks to establish a robust experimental platform enabling rapid, large-scale screening of novel, emerging or repurposed drugs to identify effective therapies for JEB.

Potential impact on people with sight loss

This project will speed up the search for new treatments that protect against sight loss in JEB and related corneal diseases. By the end of the PhD, we will have a platform that can test drugs and gene therapies using engineered human eye models. Promising treatments could be identified faster, at lower cost, and with less reliance on animal testing. These findings may lead to new therapies within five to eight years for people at risk of vision loss. Beyond JEB, the research will also deepen understanding of wound healing and age-related damage in the eye.