University of Newcastle upon Tyne

University of Newcastle upon Tyne

Newcastle University
King's Gate
Newcastle upon Tyne
United Kingdom

Project Leader

Prof. Tim Goodship

Project Staff

Dr. David Kavanagh
Senior Lecturer in Nephrology

Dr. Kevin Marchbank
Lecturer in Nephrology

Institute Presentation

The tasks attributed in this project will be undertaken within the Institutes of Genetic and Cellular Medicine (IGM  and ICM) at Newcastle University. Within the IGM Prof. Tim Goodship has since the mid 1990s undertaken a series of studies in which abnormalities affecting genes encoding both regulators and activators of the alternative complement pathway have been implicated in the pathogenesis of aHUS.  During this time he has established a registry of over 400 aHUS patients including a biobank of DNA and serum samples. Within the UK renal rare disease registry (RaDaR) he has helped to establish a comprehensive registry and biobank from UK patients with MPGN.

His laboratory was the first to establish linkage to the RCA (regulation of complement activation) cluster of genes at 1q32 (Warwicker et al, Kidney Int 1998), the first to identify mutations in the soluble complement regulator factor H (CFH) (Warwicker et al, Kidney Int 1998), the first to demonstrate clustering of  CFH  mutations  in the C terminal exons (Richards et al, Am J Hum Genet 2001), the first to identify mutations in the transmembrane complement regulator membrane cofactor protein (Richards et al, PNAS 2003), the first to identify novel hybrid complement genes associated with aHUS (Venables et al, PLoS Med 2006, Francis et al, Blood 2011), the first to show that a deletion in the RCA cluster was disease predisposing (Zipfel et al, PLoS Genet 2007) and the first to identify mutations in C3 (Fremeaux-Bacchi et al, Blood 2008).

The IGM at Newcastle University is equipped to undertake all the genetic tasks attributed in this project.  The techniques necessary for sequencing (Sanger, next generation, whole exome, whole genome), identification of genomic disorders (MLPA, array CGH) and genotyping are available on a range of platforms including high performance next generation sequencers such as the Roche Genome Sequencer FLX. Sequencing of CFH, CFI, CD46, C3 and CFB is now undertaken using this platform.

Within the ICM Dr. Kevin Marchbank has established assays for the detection of autoantibodies to factor H (Moore et al, Blood 2010; Dhillon et al, Invest Opthalmol Vis Sci 2011) and factor I (Kavanagh et al, Clin J Am Soc Nephrol 2012). He has also established assays to define the binding site and functionality of such autoantibodies.