Our Research Interests
We are interested in understanding the basic mechanisms of muscle development. We use the fruit fly, Drosophila melanogaster, as our model system, because it contains the same basic genetic tool box to make muscles as do mammals. Thus, by understanding how muscles form in flies, we can gain insight into homologous processes in vertebrates. We use a combination of genetics, cell biology, biochemistry and simple behavioural assays in our laboratory.
One focus in the laboratory is to understand how the complex skeletal muscles in the adult fly are formed. Different muscles that have different physiological functions show great variation in structure and protein isoform composition. We aim to define how master regulatory proteins, such as transcription factors, control the formation of one muscle type versus another. In a recent paper (http://www.sciencedirect.com/science/article/pii/S1534580712003723), we showed that it was possible to transform one muscle fiber into another by controlling the expression of just two genes. We are now working to understand the regulatory network through which this fundamental change occurs.
We also investigate how the heart is formed in the fly. Drosophila has a primitive heart tube called the dorsal vessel, that forms in response to signaling and transcriptional events that are profoundly conserved across evolutionary time. We were the first group (http://www.sciencedirect.com/science/article/pii/S0925477301005093 ) to demonstrate the functional significance of having genetically different types of cardiomyocytes, and we showed that homeotic selector genes control formation of the posterior heart (http://dev.biologists.org/content/129/21/5019.long), as well as controlling cardiac fate along the heart tube (http://www.sciencedirect.com/science/article/pii/S0925477305000596). Our current research in this area is focused upon understanding more precisely how the valves of the heart form, and the genes that impact this process.
Our research into muscle development also enables us to gain insight into muscle diseases that affect humans. We were recently the first group to show in detail that fly muscles contain a structure called the costamere. This structure is a protein sheath that protects the muscle during use, but whose function breaks down in individuals with muscular disease. A current project (**ref*) has focused upon a muscle degenerative mutant named thin. Our group collaborated to show that the thin mutation affects a gene that is conserved in humans. Amazingly, mutations of the human homolog cause a form of Limb Girdle Muscular Dystrophy, perhaps by affecting the function of the costamere.