Daniel St Johnston PhD FRS FMedSci, Chairman, Professor of Developmental Genetics in the Department of Genetics.
Cell polarity, the cytoskeleton and mRNA localisation
Cell polarity is essential for most cell functions 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 use Drosophila and mammalian tissue culture cells to analyse how cells become polarised and how this polarity controls the organisation of the cytoskeleton and intracellular trafficking.
Much of our work focuses on apical-basal polarity in epithelial cells, since these are the most common animal cell-type and must polarise to adhere to each other to form sheets of cells that act as barriers between compartments. As a model, we use the follicle cells that surround the developing egg chamber, as these form a typical secretory epithelium that is continuously generated from adult stem cells, making it easy to produce mutant clones. We are screening for novel polarity factors and investigating how cortical polarity controls spindle orientation, the organisation of the microtubule cytoskeleton and polarised secretion. We are also investigating polarity in the adult midgut, an absorptive epithelium, in which apical-basal arrangement of intercellular junctions is different.
In parallel, we are examining how the Drosophila oocyte is polarised, 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 use genetic, proteomic and biochemical approaches to elucidate how conserved polarity proteins regulate the organisation of the microtubule cytoskeleton in the oocyte, and analyse the mechanisms of mRNA transport and nuclear movement by making time-lapse films of moving mRNA particles and microtubule end markers in wildtype and mutant oocytes.
• Zhao T, Graham O, Raposo A and St Johnston D (2012) Growing microtubules push the oocyte nucleus to polarize the Drosophila dorsal-ventral axis. Science, 336, 999-1003.
• St Johnston D (2012) Using mutants, knockdowns, and transgenesis to investigate gene function in Drosophila. WiRES Developmental Biology, doi: 10.1002/wdev.101.
• Rees JS, Lowe N, Armean IM, Roote J, Johnson G, Drummond E, Spriggs H, Ryder E, Russell S, St Johnston D and Lilley KS (2011) In vivo analysis of proteomes and interactomes using Parallel Affinity Capture (iPAC) coupled to mass spectrometry. Molecular Cell Proteomics, 10, M110 002386.
• St Johnston D and Sanson B (2011) Epithelial polarity and morphogenesis. Current Opinion in Cell Biology, 23, 540?546.
• Chang CW, Nashchekin D, Wheatley L, Irion U, Dahlgaard K, Montague TG, Hall J and St Johnston D (2011) Anterior-posterior axis specification in Drosophila oocytes: identification of novel bicoid and oskar mRNA localisation factors. Genetics, 188: 883-898