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Summer Studentships 2022 Sarah Orr

Researcher: Sarah Orr

Location: Newcastle University

2022 Summer Studentship winner Sarah Orr, studying at Newcastle University, was awarded £2,005 for her project to develop techniques using patient-derived cells to study cystic kidney disease

The problem

Cystic kidney disease is a term used to describe a group of conditions which cause excess cysts in the kidney. Autosomal dominant polycystic kidney disease is the most common genetic kidney disease and it can be caused by several different genetic abnormalities which makes it tricky to diagnose. However, the most common genetic abnormality which causes this disease is in a gene that codes for a protein called polycystin. This affects the tiny hair-like structures, called cilia, found on the surface of some cells, including cells present in the kidney. Multiple cysts grow in the kidney and it can become enlarged, up to 3-4 times the size of a healthy kidney. Whilst this is not a cancerous change it can cause kidney damage and lead to kidney failure, most commonly during middle age, leading to the need for dialysis and a kidney transplant.

Autosomal dominant polycystic kidney disease affects about 1 in 800 people in the UK and is diagnosed through ultrasound scans. The effects and genetic cause of the disease vary from case to case, so specific tools to study, understand and monitor the condition in individual patients has the potential to lead to the development of personalised models and treatment plans, and reduce reliance on animal research in the area.

The project

In her summer studentship project, Sarah is utilising a method pioneered by the Sayer lab, which analyses the ciliary phenotype (physical characteristics of the cilia) on kidney (renal) cells collected from patient urine samples. She will be using the technique to culture cells from patients that have a specific mutation of a gene recently linked to a higher incidence of autosomal dominant polycystic kidney disease, called IFT140. She will culture the patients’ renal cells in order to study the cilia on the cells and record characteristics and measurements including their length, shape and the amount of polycystin protein they contain. These parameters could potentially be used in the future as biomarkers to indicate the presence of the disease in non-invasive urine screening for patients and allow the collection of genetic information to confirm this without invasive blood tests.

The potential

Multiple mouse models of inherited kidney disease are used in research to explore disease mechanisms and potential treatments. As with many conditions, the use of genetically altered mice allows the precise control of genetic factors, however, the models commonly do not mimic kidney disease progression in people. Modern large-scale projects and population studies for collecting human genetic information provide useful, accurate human data reflecting a diverse population for scientific study. This can be used to inform our understanding of the mechanisms of disease development and how they present and progress in different people.

This technique provides patient-specific tissue samples, which would also allow the culture of cells to help develop personalised treatments. Not only does this project offer a human-relevant pathway for the study of autosomal dominant polycystic kidney disease, it offers an alternative pathway for studying genetic elements of the condition without reliance on genetically altered mice models and the associated scientific, ethical and welfare concerns associated with developing and using these ‘humanised’ animals

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