Welcome to the Department of Biochemistry, part of the University of Oxford's Medical Sciences Division. We are one of the largest Biochemistry departments in the world and carry out world-class research and teaching. Our researchers come from a range of disciplines and work in a collaborative environment on all aspects of modern molecular and cellular biochemistry. We hope you enjoy reading more about our activities on these pages.
Professor Mark Sansom, Head of Department
New method allows researchers to explore how fibrillin is assembled
Researchers in the department have shed light on the early stages of assembly of fibrillin into microfibrils, a major component of the elastic tissue of animals.
Fibrillin microfibrils form beaded filament structures (blue) in the extracellular matrix of tissues such as in the elastic laminae of the aorta. Click photo to enlarge.
The research from Professor Penny Handford's lab, with lead author Dr Sacha Jensen, is published in PNAS (1).
The work provides an important step in understanding how the extracellular matrix assemblies of microfibrils are constructed and how mutant fibrillin associated with human disorders behaves.
Fibrillins are a group of large, disulphide-rich molecules dominated by calcium-binding EGF-like (cbEGF) domains. Fibrillin monomers are assembled into microfibrils at the cell surface and are quickly cross-linked into the extracellular matrix. Here they contribute to the elastic properties of tissues such as blood vessels.
Unlike collagen, the other major connective tissue protein, fibrillin cannot be assembled in vitro. This has hampered studies of microfibril assembly and its regulation, which would be valuable in understanding how mutations in the fibrillin gene cause a number of human disorders such as Marfan Syndrome (MFS).
Dr Jensen and colleagues wanted to develop a cellular system that would allow them to investigate microfibril assembly. Using information from previous structural studies of the N-terminal domains of fibrillin-1 (2), they engineered a GFP-tagged version of the protein, inserting GFP into a flexible, glycine-rich region where it would not affect the behaviour of the protein.