Membrane and cytoskeletal dynamics in morphogenesis and disease
We use an integrated approach combining cell biology with biochemistry and biophysics to look at vesicle formation, secretory cargo selection, motor protein driven transport, and cell organization. All of our work uses various aspects of advanced imaging of fixed and living cells, including nanometre tracking, 3D rendering and deconvolution, as well as electron microscopy (with the Verkade lab) and zebrafish (with the Martin lab). In particular, my lab is investigating the role of motor proteins in membrane positioning, cargo sorting, and vesicle trafficking, as well as asking fundamental questions about how and why the intracellular membranes of mammalian cells are organized as they are. We have an excellent collaboration with the lab of Pete Cullen with regard to the role of motors in endosomal sorting. We are also working to elucidate the role of Sec16 in the organization of metazoan ER exit sites, notably on exit from mitosis.
Our latest work combines our experience in vesicle coat function in membrane trafficking, and motor protein-based organelle movement to study the formation and function of primary cilia. These organelles, found on nearly all cells are essential for normal animal development. Defects in cilia formation and function cause many human diseases. Our work is based on exciting preliminary data that link the Golgi to the formation of the cilium through interaction of Golgi membranes with the ciliary dynein motor. A key aspect of our work seeks to define the molecular mechanisms that link Golgi and dynein function at the earliest stages of cilia formation. This work has significant potential to enhance our understanding of this fundamental process during normal development as well as human disease.
The lab uses a combination of biochemical and cell biology techniques, notably advanced microscopy techniques to examine these processes in living (and fixed) cells. This includes nanometre tracking of objects, semi-automated 96-well plate screening, deconvolution and 3D reconstruction, and electron microscopy. More and more of our work is directed towards physiologically relevant systems, in particular, 3D culture of polarized cells and primary cell cultures, and we are now using the model organism zebrafish to address key areas of membrane trafficking in a whole organism.
Some images showing examples of our recent work
David Asante, Dylan Bergen, Sylvie Hunt, Vicky Miller, Anna Townley.
Stephens DJ. (2012) Functional coupling of microtubules to membranes: implications for membrane structure and dynamics. Journal of Cell Science. 125: 2795-2804.
Stephens DJ. (2012) Cell Biology: Collagen secretion explained. Nature. 482: 474–475.
Townley AK, Schmidt K, Hodgson L, Stephens DJ. (2012) Epithelial organization and cyst lumen expansion require efficient Sec13–Sec31-driven secretion. Journal of Cell Science. 125: 673-684.
Budnik A, Heesom KJ, Stephens DJ. (2011) Characterization of human Sec16B: indications of specialized, non-redundant functions. Scientific Reports. 1: 77.