Research Interests

Cilia, Extracellular matrix, Membrane traffic, Microtubule cytoskeleton, Microscopy

My lab is undertaking a focussed research programme studying the organisation and function of the early secretory pathway in mammalian cells. My current research focuses on the function, regulation and organisation of the early secretory pathway. A particular focus of this work is to define how and why mammalian cells are organized in the way that they are; our work seeks to define how intracellular patterning underlies function, and more importantly dysfunction, in human disease. More recently, our interests have evolved to include the trafficking of proteins to and within cilia. In this context we have been working to understand the composition and function of the cytoplasmic dynein-2 motor and its relationship to the formation and function of primary cilia.

The core technical basis of our work is multidimensional live cell imaging and I have considerable experience in the application of wide-field and confocal techniques to the study of living cells. Our work is focussed on the generation and maintenance of the organisation of the pathway, how it is coordinated with cytoskeleton and motor protein function, and how these processes are regulated by protein phosphorylation. In particular, my lab is investigating the functional organisation of the early secretory pathway and the role of microtubule motors in membrane traffic. More specifically this relates to the mechanisms of formation and function of primary cilia and the secretion of procollagen. Several of the projects in my lab are of direct clinical relevance and we are constantly developing our capabilities, recently including zebrafish genetics and electron microscopy (including immunogold labelling of ultrathin cryosections and tomography).

Our latest work develops our findings from cell biology assays into more physiological contexts including multicellular systems (e.g. cysts grown in 3D matrix) and zebrafish development. These systems form the core approach to our ongoing work which aims to develop our knowledge of COPII-dependent secretion with cell and tissue morphogenesis as well as provide stronger relevance to human disease.

Lab website http://stephenslab.wordpress.com/