Working life: Richard Coward
Dr Richard Coward is an MRC Senior Clinical Fellow and Head of Research for the School of Clinical Sciences at the University of Bristol. Here he tells us about his working life from spending time with ‘beautiful’ cells to working with the pharmaceutical industry.
My MRC Senior Clinical Scientist Fellowship enables me to combine clinical and basic scientific work, allowing me to continue my laboratory and research interests as well as my clinical commitment to paediatric nephrology.
I was attracted to research at the end of my clinical training. The drive to do this was because I looked after a patient who had an inherited condition called congenital nephrotic syndrome, a disorder passed down through families in which a baby develops massive amounts of protein in the urine.
Soon afterwards it became clear that the podocyte cell, a beautiful cell in the glomerulus ― the filtering unit of the kidney ― that looks like a big octopus, was involved. The gene responsible for the disorder was discovered to code for a protein located exclusively in the podocyte.
This motivated me to undertake a PhD studying the molecular biology of the podocyte. The kidney is the world’s most sophisticated filter, processing around 180 litres of water and small molecules per day. In early stage kidney disease the filter can break down, which can cause essential plasma proteins to leak into the urine and lead to end-stage renal failure (ESRF). Diabetic kidney disease is the leading cause of ESRF in the developed world and podocyte loss is a predictor of progression into ESRF.
During my PhD I studied a condition called acquired nephrotic syndrome, however on discovering that podocyte cells were sensitive to insulin, I changed my research focus towards the insulin-signalling pathway in the podocyte and its relevance to kidney disease.
In 2006 I secured an MRC Clinician Scientist Fellowship, which enabled me and my family to relocate to Canada, to work in the world-leading glomerular laboratory in Toronto, with Professor Susan Quaggin. There I made a model of podocyte insulin resistance in a functional glomerulus. By making changes to specific genes coding for the major receptor for insulin in transgenic mice, I produced insulin receptor-deficient podocytes.
This caused the mice to develop kidney disease, revealing that the podocyte needs to be insulin sensitive to work normally and prevent protein from leaking into the urine.
In 2013 I was awarded an MRC Senior Clinical Fellowship which has allowed me to reduce my clinical commitment, consolidate my research and develop my research team.
Four weeks per year I still look after the acute admissions of children from the South West of England with renal problems, including acute kidney injury requiring dialysis, as well as children undergoing kidney transplantation. Furthermore I run a clinic in which I see children with long-term kidney problems who I have been looking after for many years now.
I really like being able to maintain contact with patients, but it gives me the flexibility to not be overburdened with a lot of clinical work that would be detrimental to the research. I find the clinical work really helpful as is it informs me of the important, clinically relevant, scientific questions that need to be answered.
A good clinical example is a disorder called haemolytic uremic syndrome. This usually occurs when an infection in the digestive system produces toxic substances that attack small blood vessels causing kidney injury, and in some cases involves the brain and other organs of the body.
It is the leading cause of acute kidney failure in children and has an associated mortality rate of approximately 5 per cent. We think the podocyte may be involved in this process. In an attempt to prove this ― with the help of an MRC-funded Clinical PhD Fellowship ― we have developed a transgenic mouse to mimic this system.
After returning from Canada I wanted to look at the insulin pathway in more detail and make my research more translational by looking at therapeutic targets. Because my work has gone well, I have been invited to give talks in different parts of the world including Melbourne, Australia. At the end of my presentation there, someone from pharmaceutical company Novo Nordisk came up to me and said they had enjoyed the talk. We started talking, I went over to visit them in Copenhagen and it has since developed into a postdoctoral academic fellowship.
Novo Nordisk are excellent collaborators because they’re the biggest producers of insulin in the world. They have a great deal of experience and expertise in the insulin and insulin like growth factor signalling pathways which is very relevant to my research. We want to develop models to work out how important insulin signalling is in diabetic kidney disease in humans. I’ve got full freedom to publish whatever we find and I’ve got a very experienced postdoc, funded by Novo Nordisk.
Our good relationship with industry is driven by funders like the MRC looking favourably on people trying to work together with industry, to translate the benefit of basic scientific discoveries into new therapies to benefit patients and society.
As told to Isabel Baker.