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Research in the lab is directed towards an understanding of the cellular activities that underlie the development of epithelial tissues and in particular towards the role played by cell interactions in the regulation of these activities. Our longer term aim is to focus on the interdependence of cellular events and the way in which they are co-ordinated to produce a mature tissue of defined size and shape, in which the patterned differentiation of cells forms a functionally integrated structure. A particular interest is to understand how the physiological attributes of a tissue are defined during development.
With this view in mind, we have chosen to work on the embryogenesis of a very simple transporting epithelium, the Malpighian tubules of the fruit fly, Drosophila melanogaster.
The reason for choosing the Malpighian tubules as a model system is that the tissue develops in discrete stages - the initial allocation of primordial cells, which then proliferate and subsequently rearrange to form a tubular, single cell-layered epithelium before final cell differentiation.
General reviews
By choosing specific periods of embryogenesis, it is therefore possible to study the regulation of particular cell activities in isolation of others and to analyse the coordination of particular events in a linear sequence. A unique advantage of the Malpighian tubules is that their physiological maturation can be followed by the deposition of a visible excretory product, uric acid, and that the parameters of their physiological activity, as well as the activity of specific cell types within the epithelium, can be analysed in vitro. The use of the Drosophila embryo as an experimental organism allows analysis at both the cellular and molecular level, so that the molecules underlying cellular activities can be isolated and characterised and their precise roles analysed in mutants in which the functions of particular molecules are lost.
Using this system, we are investigating the genetic, molecular and cellular basis of the coordination of critical stages in epithelial development.
To look at the projects currently underway in the lab please go here
About our work.....
An essential feature of our work is that it is multidisciplinary. By bringing together approaches, which allow a combined analysis of molecular genetic, cell biological and physiological parameters, we aim to show how functional differentiation is controlled and coordinated.
Genome projects provide ready access to a wealth of sequence and expression data for many new genes. The challenge now is to understand how genes are deployed and their activities integrated to orchestrate the cellular events involved in the generation and physiological activity of tissues. This information will come from detailed studies of the molecular basis of subcellular events in tissues such as Drosophila Malpighian tubules, in which molecular genetics, cell biological analysis, the experimental manipulation of cells and in vitro physiological analysis can be combined. While the immediate outcome of our research will be a deeper understanding of the molecular and cellular processes that underlie the assembly of Malpighian tubules, our analysis is likely to reveal mechanisms that are fundamental to the generation of transporting epithelia, since these physiologically crucial tissues share many common features.
