Bioinformatics approaches to understand mechanisms of disease of cardiovascular disease

As reported by the Global Burden of Disease Study, kidney disease is one of the fastest rising causes of mortality worldwide, claiming 1.1 million lives per year. A myriad of factors can lead to kidney damage; as a vital organ filtering approximately 180 litres of blood per day, a decline in kidney function is swiftly followed by a decline in health and eventually death. The elucidation of the physiology of the kidney will enable the development of improved therapies and treatments for managing kidney diseases.

Research Methods and Objectives

A late stage indicator of kidney disease is proteinuria, and key feature connecting many kidney diseases is damage to podocyte cells. Podocytes are highly specialised cells which envelope the glomerular capillaries and form part of a selective barrier, acting to ensure the retention of larger proteins within the lumen of the capillaries of which they encapsulate.

This project aims to combine wet laboratory work, researching and improving what is known regarding podocyte physiology, and a bioinformatics approach, to elucidate the pathways and interactions of podocyte cells. A bioinformatics networking model comprising interconnecting data will be created, allowing information to be displayed in a format which is interactive, accessible and highly data rich. Creation of such a network model will enable visualisation of the data generated in novel ways, which would not possible with graphs, and images alone. It will allow for the

identification of discrepancies in metabolic pathways and intra and inter cellular communications, and will contribute to the little that is currently known about podocytes. This project also aims to enable the identification of earlier markers for kidney damage and therefore contribute to the generation of new therapies for treating the condition.

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Image of Zebrafish treated with puromycin
Image of Zebrafish treated with puromycin. From Seb’s Glomerular injury paper. 2017 –(Sebastien Andrew Rider, Finnius Austin Bruton, Richard George Collins, Bryan Ronald Conway, 2017)
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Schematic of podocyte foot processes, and podocytes enveloping a capillary
Schematic of podocyte foot processes, and podocytes enveloping a capillary. (c) Courses lumen learning

Investigators

Cara Brown (BHF Student), John Mullins, Tom Freeman, Bryan Conway, Linda Mullins