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Extracellular Biology: Structure and Signalling


Welcome to the webpage of the laboratory of Professor Penny Handford.

We are a research group in the Laboratory of Genes and Development in the Oxford University Department of Biochemistry.


Our research

The EGF domain is a widely distributed disulphide-rich structural motif in extracellular proteins. A subset of EGFs contain a calcium binding site (cbEGF domain) which confers structural rigidity, often facilitating protein-protein/proteoglycan interactions. Missense mutations which alter residues within the domain are associated with a diverse collection of human diseases highlighting the key role of the EGF/cbEGF domain in a variety of biological processes including connective tissue function, blood clotting, cholesterol metabolism, determination of cell fate and maintenance of stem cells.

We have developed biochemical, biophysical, genetic and cell biology methods to understand native domain architecture and function, and molecular pathology associated with this family of proteins. This has given new insight into structure/function relationships and molecular mechanisms underlying haemophilia B, cutis laxa, age-related macular degeneration, Alagille syndrome, Marfan syndrome, Stiff skin syndrome.

We currently have two main areas of interest:

1) Notch receptor and its ligands Serrate/Jagged and Delta/Delta-like

2) Connective tissue proteins fibrillins and LTBPs

News

July '14:
Sacha Jensen’s research into the role of the C-terminal propeptide of Fibrillin-1 is published in PNAS (please visit our publications page, reference 84).

Penny, Bogusia and Laurie travel to the USA to present a poster at the Gordon Research Seminar/Gordon Research Conference “Notch Signalling in Development, Regeneration and Disease”.

May ‘14:
Paul Taylor’s DPhil research studying the effects of glycosylation on the Notch/ligand interaction is published in PNAS (please visit our publications page, reference 83).

November‘13:
Mouli Chillakuri’s work on the human Notch ligand Jagged1 is published in Cell Reports (please visit our publications page, reference 79). A collaborative effort with Susan Lea’s group identified for the first time a calcium-dependant phosopholipid-binding C2 domain at the N-terminus of Jagged1. This exciting discovery is the subject of a commentary by Stephen Blacklow (Blacklow SC. Refining a Jagged Edge. Structure. 2013 Dec 3;21(12):2100-1).

© 2012 Penny Handford