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UCL Division of Biosciences

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Prof Stephen Perkins

Prof Stephen Perkins

Professor of Structural Biochemistry

Structural & Molecular Biology

Div of Biosciences

Joined UCL
1st Nov 1986

Research summary

In molecular medicine, protein three-dimensional structures are invaluable for elucidating functional mechanisms and the effect of disease-causing mutations. We have worked for many years on antibodies and the complement proteins with immunologists, and collaborate with clinical biochemists that need protein structures to support their research.

The complement system provides a major non-adaptive immune defence mechanism for its host. It is activated in response to the challenge of foreign material in plasma. Complement activation proceeds through a series of limited proteolytic steps in one of three pathways, the alternative, classical or lectin. Once the central protein C3 is activated to C3b, this activates more C3. Regulation of C3b by molecules such as Factor H is essential for an appropriate complement response. We have looked at many of the complement proteins, such as Factor H, C3 and CR2.

Age-related macular degeneration (AMD) causes loss of central vision and accounts for 50% of blind registration in the Western World, mostly in the over-50 age group. A key feature of AMD is the presence of drusen that are extra-cellular deposits between Bruch's membrane and the retinal pigment epithelium. The accumulation of drusen-associated molecules suggests a complement attack. A single point mutation in Factor H at Tyr402His is associated with many AMD cases. This is proximate to binding sites for several ligands such as heparin and C-reactive protein. Other ligand-binding regions of Factor H are associated with kidney failure, most notably atypical haemolytic uraemic syndrome. Scattering and ultracentrifugation methods are powerful tools for understanding the role of Factor H, and we have performed many studies with Factor H. See http://www.fh-hus.org

Teaching summary

I am course organiser for BIOC2002 and BIOC2003, two second year undergraduate Biochemistry courses. I am Chair of the Biochemistry Exam Board from 2013 onwards.

I also teach protein structures to medical students, both in lectures and in a Student Selected Component.

Education

University of Oxford
DPhil, Molecular Biophysics | 1977
University of Oxford
BSc, Chemistry and Biochemistry | 1973

Biography

I obtained my BA in Chemistry and my DPhil in Molecular Biophysics from Oxford University. I obtained EMBO and EMBL Fellowships to work at the ETH-Zurich and at EMBL-Grenoble. I was awarded a Lister Fellowship held at the Kennedy Institute of Rheumatology, Hammersmith, London.

I was then appointed to a Wellcome Trust Lecturership at the Royal Free Hospital School of Medicine, and obtained my Personal Chair in 1998 at the same same as this merged with UCL. I moved to the main campus of UCL in 2002.

I have published over 200 papers, mostly in the field of structural immunology applied to the five human antibody classes and to the complement proteins of innate immunity.

Publications