Projects and Research Interests

Brief Overview of Current Research in the Lab:

Cell polarity is essential both for cell function and for several key developmental processes, such as cell migration, axis determination and asymmetric cell division, whereas loss of polarity is a critical step in the formation of tumours. We use Drosophila to analyse how cells become polarised, using a combination of cell-biological, genetic and molecular approaches.

Much of our work uses the oocyte as a model, since the localisation of bicoid and oskar mRNAs to opposite ends of this very large cell defines the anterior-posterior axis of the embryo. We are using proteomic and biochemical approaches to elucidate how conserved polarity proteins regulate the organisation of the cytoskeleton, and we are investigating the mechanisms of mRNA transport by making time-lapse movies of mRNA particles in wildtype and mutant oocytes. We are also performing large scale screens for mutants that affect the localisations of bicoid and oskar mRNAs, and are analysing novel polarity and mRNA localisation factors that these identify.

In parallel, we are examining how the apical-basal polarity of epithelial cells is established using the follicle cells and the adult gut as models. We have recently discovered that the tumour suppressor, LKB1, and the energy sensor, AMPK, are specifically required for epithelial polarity under conditions of energetic stress, revealing the existence of a distinct low energy polarity pathway. We have now identified several other components of this pathway, all of which have also been implicated in cancer. We are therefore performing RNAi screens for new genes that are required for polarity under either high or low energy conditions.

 

RNA Localisation:

The intracellular localisation of mRNAs is a general mechanism to target proteins to the regions of a cell where they are required, and plays an important role in the polarisation of many cell types. A striking example of this phenomenon is provided by the Drosophila oocyte, where the localisation of bicoid, oskar, and gurken mRNAs to three distinct positions within the cell determines the polarity of the anterior-posterior and dorsal-ventral axes of the embryo. Using the powerful genetics of Drosophila , we are using a combination of molecular, cell-biological and genetic techniques to investigate the mechanism of mRNA localisation. In addition, we are studying how the two axes of the oocyte become polarised to define the destination of these transcripts, in order to understand the origin of polarity in Drosophila development.

For more images click HERE and for our publication list click HERE

For an overview of the projects the lab has previously been interested in, see:

St Johnston, D. The Begining of the end. EMBOJ 2001 Nov 15;20(6169-79) | Full Text | Pumbed |

(Last updated 3/6/2008)