Membranes & Sorting

BIOGRAPHY

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.
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 ER-to-Golgi transport with specific reference to the macromolecular coat protein complexes, COPI and COPII. 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).

I am continuing to develop approaches to multidimensional live cell imaging both in terms of hardware (such as the application of super-resolution imaging techniques that go beyond the classical diffraction “limit”), software (both commercial and developed ourselves for object tracking and image quantitation), and specific reagents (organelle labels) to extend our current imaging capabilities. Our work also combines high-content screening on 96 well plates and chemical biology approaches. These developments have included published collaborations internationally (e.g. Japan, Germany), nationally (e.g. Warwick, London), and notably within the University of Bristol with the labs of Cullen (Biochemistry), Hudson (Chemistry); I am also pursuing our interdisciplinary work integrating Chemistry, Physics, and mathematical modelling in to our own programme. This interdisciplinarity has been highly successful to date resulting in key publications.

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.

AWARDS/HONORS:
Faculty Member of the Year winner for Cell Biology 2011