Dominant genetic disorders are notoriously difficult to cure as they require selective silencing of defective part of the gene whilst leaving the other functioning. Epidermolysis bullosa simplex (EBS) is one of many dominant genetic disorders caused by mutations in keratin intermediate filaments. Taken together, the keratin diseases incurably affect up to 1:4,000 of the population with variable degrees of severity but all affecting quality of life. EBS skin fragility (blisters upon mild friction) is distressing and incapacitating. In spite of our knowledge of the keratin mutations that lead to the development of EBS, there are several aspects that are still not well understood. One of these is the phenomenon reported by many people with EBS of temporary improvement in blistering during periods of fever. There are two plausible mechanisms for this, giving rise to two theories that will be investigated.

Theory 1: that the mutant keratin protein is selectively eliminated during fever, due to the fact that it is more poorly assembled into filaments at higher temperature and, therefore, seen as "rubbish" by the cell.

Theory 2: that the body’s response to stress, such as fever, results in the production of molecules that cause extra keratins to be produced, which may reinforce the fragile skin cells.

These ideas will be tested by studying skin cells with EBS keratin mutations. Cells will be subjected to changes in temperature and exposure to molecules known to produce keratins. The effects on the cells will be measured and, if specific responses can be identified, attempts will be made to identify potential drug compounds that trigger such responses selectively and accurately.