MRC DTP in Precision Medicine

The role of the human SMOC2 gene in kidney fibrosis and host defence against human African trypanosomiasis

Supervisors

Prof Annette MacLeod, School of Biodiversity, One Health & Veterinary Medicine, University of Glasgow
Dr Paul Capewell, School of Molecular Biosciences, University of Glasgow

Summary

Chronic Kidney Disease (CKD) has been described as an epidemic, affecting 12% of all adults in the US, and over 7 million in the UK, with persons of African heritage at increased risk. This partly due to a significant association between CKD and high-risk variants of genes carried by 35% of the African American population. It has been proposed that this is part of an evolutionary trade-off against Human African Trypanosomiasis (HAT) disease, caused by the parasitic Trypansoma brucei, which remains a major public health threat across sub-Saharan Africa. Several genes have been associated with these defence mechanisms, including SMOC2, a gene typically characterized by roles in wound repair and tissue fibrosis.

Based at the University of Glasgow, with links to Edinburgh, this project aims to dramatically increase understanding of the role of SMOC2 in the body through two related approaches. First, the project will investigate the role of SMOC2 in defences against the T.brucei pathogen.
Second, it will investigate SMOC2’s role both in the development of CKD and precursor kidney fibrosis, through examining the impact of SMOC2 over and under-expression in vivo, to determine its impact on pro-fibrotic signalling pathways.

By collaborating with leading researchers and utilizing genomic data, the project will seek to develop new avenues of research for the potential evolutionary trade-off associated with defences against HAT.