SUMMARY OF RESEARCH BEING UNDERTAKEN

The proteins known as keratins found in skin and other tissues of the body are members of the intermediate filament family of proteins, which all form webs or meshes of filaments inside cells to reinforce them against physical wear and tear. It is now well established that mutations (defects) in the keratin of skin cells can lead to cell fragility and the characteristic blistering of EB simplex. This knowledge has allowed the research group to identify the mutations in affected families that cause EBS and to carry out prenatal diagnosis where required.

However, in order to be able to cure or improve these skin fragility problems, it is necessary to understand more specifically how the tissue fragility arises, i.e. how and why the mutations that have been identified cause the keratin filaments to fail. Once this information is available, we may begin to design treatments that lessen the fragility.

In this project the team propose to analyse the properties of cells affected by EBS mutations to learn how their weaknesses can be overcome. The breakdown of mutant keratin filaments in cells under stress will be investigated using techniques that deform cells, including a machine that physically stretches cells grown in the laboratory to mimic the skin stress that causes blistering in EBS. Changes in the keratin filaments during this stress will be monitored and the biochemical changes in the cells documented. Using this information, the team will seek to find compounds that could become potential medications to reduce keratin breakdown and, thereby, reduce the fragility of the skin of EBS patients.