Grant: Operating Grant

Genes can be regulated at many different levels. Best understood are the machineries that make a messenger RNA (mRNA) copy from the DNA and then translate the information encoded in the mRNA into protein. It is well known that cells are instructed to take on different fates (skin, nerves, muscle, etc.) during development in large part through different genes being turned 'on' or 'off' in their ability to make mRNA. Recently it has become clear that a great deal of control is exerted, not in the making of the mRNA, but also after the mRNA is made. For example, an mRNA may be made in two cell types (say nerve and muscle) but only be allowed to be translated into protein one of these (say, nerves). Likewise the mRNA may be produced in both cell types but its stability may be regulated such that it is chewed up and eliminated in one cell type but not the other. Furthermore, where an mRNA is placed within a cell is very important and highly controlled and can ensure that the protein is made in the right part of the cell (say in the axon of a nerve rather than in its dendrites). Defects in these sorts of processes - called post-transcriptional processes - can lead to developmental defects and disease. The machinery of post-transcriptional processes is evolutionarily highly conserved so that fruit flies and humans have very similar machinery. We use the fruit fly - which is amenable to highly sophisticated molecular, cellular and genetic methods - to understand the post-transcriptional machinery and its role in development and disease.