Understanding ER, Golgi and cilia function and their relationship to the extracellular matrix.

Cells are the fundamental unit of life. Our aim is to understand cell function in the context of membrane and cytoskeleton dynamics.

Our work addresses three overlapping areas: secretory pathway function, membrane-microtubule dynamics, and formation and function or primary cilia. 

The lab specialises in the analysis of membrane traffic in mammalian cells using advanced light microscopy techniques, in particular, the imaging of living cells. Our work includes developing imaging technologies and integrating model systems including 3D cultures and zebrafish to develop our research. The lab itself is using high-resolution light microscopy of living cells, notably live cell imaging, in 3D over time, to examine the organisation and function of the mammalian secretory pathway both in healthy cells as well as in disease states. In this regard our work focuses on collagen secretion and the formation and function of primary cilia. Our work is very much in the Fundamental Bioscience space, seeking to define new understanding of these complex systems. Ultimately we work to explore these systems in biomedical contexts.

We are part of the School of Biochemistry at the University of Bristol. The lab is a key part of a strong cell biology focus of the Faculty which includes excellent facilities for microscopy, proteomics and high performance computing. We work closely with other Cell Biology labs in the University as part of a cohesive network of researchers with common interests. This network of labs includes those of Pete Cullen, Harry Mellor, Girish Ram Mali, Mark Dodding, Helen Weavers, Bernadette Carroll, Adam Grieve, Jon Lane, Paul Verkade, and Paul Martin. This grouping forms a highly collegiate network through which staff and students interact on multiple levels from informal discussion to full collaboration; it also forms the basis for our Wellcome Trust 4 Year PhD Programme in Dynamic Cell Biology.

Central to the success of our projects is the Wolfson Bioimaging Facility and our key collaborations with other labs.

Ours is very much a fundamental science approach to biomedical research. The biggest challenges facing us are how to define the molecular machinery involved at the nano-scale but also at the level of more complex systems, whether that means intact cells or developing organisms.

Consequently, we are exploiting methodologies that include imaging at high-resolution – nanometre tracking of fluorescent objects, electron microscopy, TIRF microscopy, deconvolution and 3D reconstruction. We are of course exploiting gene editing and new proteomic technologies to develop our work. Each technology is applied as required to a specific biological problem. The biology drives the technology in every case. These tools enable us to define the molecular basis of cellular function which we now ally to other tools from relevant cell culture models to zebrafish genetic experiments. All of our projects seek to define the molecular basis for membrane and cytoskeleton function in cells. Our aim is that integrated approach (“from nano- to Danio”) will give better progress towards our goals.

We are very grateful for continued funding from the following organizations:

 

 

 

Other key institutional infrastructure, including our main research lab and the Bioimaging Facility, were funded through the Wolfson Foundation.

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If looking to request reagents from us then please do consult Addgene for our most commonly requested plasmids.

   http://www.addgene.org/David_Stephens/

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