St Johnston Lab

Our Research

Cell polarity is essential for normal cell function and for several key developmental processes, such as cell migration, axis determination and asymmetric stem cell divisions, whereas loss of polarity is a critical step in the formation of tumours. We are using Drosophila, mouse intestinal organoids and mammalian tissue culture cells to analyse how polarity arises and how cortical polarity factors regulate other polarised aspects of cell behaviour.
Much of our work focuses on epithelia. Most organs in the body are composed of epithelial cells that are polarised along their apical-basal axes so that they can adhere to each other to form sheets of cells that act as barriers between compartments. We use the follicular epithelium that surrounds the developing Drosophila egg chamber as a model secretory epithelium, because it can be imaged along its apical-basal axis and is continuously generated from stem cells, making it easy to produce mutant clones in the adult. We are investigating how apical-basal polarity is established and how polarity factors control polarised secretion and the organisation of the microtubule cytoskeleton. For example, we have determined how cells divide so that both daughter cells remain within the epithelial layer, and have found a mechanism that pulls cells born outside the monolayer back into place. Almost all well-characterised epithelia are secretory, therefore we are using the Drosophila adult midgut as a model for an absorptive epithelium. We have found that the polarity of midgut cells relies on different polarity factors from secretory epithelia, and are now investigating how this relates to their inverted arrangement of intercellular junctions. Please click here to read more about these projects.
A Drosophila ovariole: large germ line cells surrounded by a monolayer of epithelial cells (follicle cells) stained for the polarity proteins aPKC (green), Discs Large (red) and DNA (blue)
H. Lovegrove. A Drosophila ovariole: large germ line cells surrounded by a monolayer of epithelial cells (follicle cells) stained for the polarity proteins aPKC (green), Discs Large (red) and DNA (blue).
Another major goal of the group is to understand how the Drosophila oocyte is polarised to define the anterior-posterior axis of the embryo. This requires the microtubule-dependent transport of bicoid and oskar mRNAs to opposite ends of this very large cell, and we are using a range of live imaging techniques to visualise moving mRNA particles and growing microtubules in wildtype and mutant oocytes. Please click here here to read more about these projects.
egg chamber stained with anti-tubulin antibody, illustrating microtubule organisation in the oocyte and surrounding epithelia.
D. Nashchekin. Egg chamber stained with anti-tubulin antibody. A good illustration of microtubule organisation in the oocyte and surrounding epithelia.
In addition to the above, and in conjunction with groups in Yale, Oxford and the LMB, Cambridge, members of the lab are developing super resolution microscopy tools and techniques in order to visualise polarised transport in epithelial cells. "Nanoscopy of dynamics in the living cell". Please click here to read more about these projects.
Site last updated 05/04/18