One of the long-term objectives of this project is to understand the physiological role of metallothionein. This is a small protein found, apparently, in all higher organisms (both plants and animals) and which binds, very efficiently, some highly toxic metals such as cadmium and mercury and other, essential, minerals such as zinc and copper. It is not clear whether the function of the protein is to protect the organism from the toxic metals or to store the necessary ones for delivery at times and organs where they are needed. This question will be investigated by obtaining mutants in Drosophila melanogaster which are unable to produce normal metallothionein and testing them for their sensitivity to toxic metals and their nutritional requirements with respect to zinc and copper. In order to interpret these experiments it will be necessary to study the normal processing of metals and synthesis of metallothionein in this species. Because this protein is highly conserved in evolution it is expected that the results will help understand the processing of these important metals in humans. The importance of understanding gene regulation may be incalculable with regards to a number of human disorders that extend from developmental abnormalities to cancer. The metallothionein gene offers a prime opportunity to study gene regulation becasue of its inducibility. Experiments are planned to prepare DNA sequences with alterations nearby the structural gene. These mutations will then be incorporated into the Drosophila genome and gene function tested. This will allow identification and later characterization of the regulatory sequences.
