SUMMARY OF RESEARCH BEING UNDERTAKEN

Skin is composed of two tissues, namely epidermis and dermis. The epidermis is exposed to the external environment and sticks to the underlying dermis using various adhesive mechanisms. These adhesive mechanisms include hemidesmosomes, which are button like structures tied together with threads of keratin protein. Hemidesmosomes adhere the basal epidermal cells to the basement membrane. The basement membrane can be visualised as a cement or glue formed of proteins supported by and anchored by the protein cables on to the dermis. All these buttons, glue and cables are important for the stable adhesion between the epidermis and the dermis. In some individuals, one of the proteins of these buttons or glue or cables is missing or defective and this leads to epidermolysis bullosa (EB).

The proteins are made up of small building blocks called amino acids. The information to make a protein is stored in a stretch of DNA (deoxyribonucleic acid) as a text or sequence composed of four letters, A,T,G and C. Such a stretch of DNA is called a gene. Sometimes this text in a gene is scrabled or a letter is missing or a wrong letter is added and, hence, proteins cannot be made or, if made, they are defective and cannot function properly. Such a modification in the DNA text is called a mutation. EB is the result of mutations in the genes which store the information to make keratin proteins or the protein components of hemidesmosomes or the basement membrane. So far, mutations in 10 genes are known to cause the condition. However, in some EB patients mutations in some unknown genes seem to be responsible. This project aims to find those genes, mutations in which would lead to EB.

To find those unknown gene mutations causing EB, zebrafish will be used as a model system. The adhesive mechanisms used in this small fish to tether the epidermis to dermis are very similar to those in humans and we already know that zebrafish skin blisters can arise due to mutations in certain genes. Adult zebrafish will be treated with a chemical that will introduce mutations randomly in DNA and then look for the skin blisters in their progeny. The mutated genes resulting in EB like disease in fish will be listed. These genes will then be isolated to analyse their probable function in adhering epidermolysis to dermis. It is felt that knowing all the mutated genes involved in causing EB will help scientists to develop effective tools to control and treat the condition.