The annual, international, three-day Pint of Science festival sees thousands of scientists across the world simultaneously standing up in local pubs and telling the public about their research. From 15 – 17 May 2017, students from the University of Bristol, are organising and hosting the festival at various pubs and venues across the city, including The Greenbank, The Attic Bar, Good Chemistry Brewery, The Eldon House, Roll for the Soul, Rise/Friska, The Hen and Chicken, The Steam Crane and The Kings Head (Whitehall Road).
On 17 May, Dr Carl May and his colleague Dr Gavin Welsh, will speak at sell-out event ‘Cracking the kidney disease code’, sponsored by Kidney Research UK, at The Eldon House. Dr Carl May achieved his PhD after completing a Kidney Research UK-funded studentship at the Academic Renal Unit, University of Bristol, with his thesis, titled Alterations in Podocyte Phenotype in Health and Disease, in 2014. Now a post-doctoral research assistant, funded by the Medical Research Council, Carl is investigating the role of a protein known as PAR-1 in the disease process of Focal Segmental Glomerulosclerosis – a cause of nephrotic syndrome in children and adolescents, as well as a leading cause of kidney failure in adults. Here he kindly tells us more about his research:
The kidneys are underrated – we often take them for granted. They are an incredible pair of organs that filter around 180 litres of blood each day without getting clogged. In addition to keeping the blood clean, the kidneys are also responsible for maintaining the right balance of fluid and various salts. The site of filtration within the kidney is known as the glomerulus.
I am particularly interested in a condition known as Idiopathic Nephrotic Syndrome. This is a condition that can occur spontaneously and leads to the breakdown of the filtration barrier within the kidney. There is no cure: only treatments that attempt to alleviate the symptoms and slow progression. Ultimately, Idiopathic Nephrotic Syndrome can lead to end-stage renal failure whereupon the patient will need a kidney transplant. We think that a type of cell in the kidney, known as the podocyte, is important in the disease process. There is a lot of evidence to suggest a role for a circulating factor (a particular molecule that travels in the blood stream) in Idiopathic Nephrotic Syndrome. We think that this circulating factor injures the podocyte.
In a healthy kidney, the podocyte has a beautiful, intricate architecture. It is reminiscent of an octopus that wraps its tentacles around the capillary. The tentacles of neighbouring podocytes intertwine. The gap between these neighbouring appendages is spanned by a molecular bridge known as the slit diaphragm. This forms the final layer of the Glomerular Filtration Barrier. In disease, the tentacles of the podocyte retract. In this state, they no longer contribute to the function of the sieve.
At Bristol Renal, we want to learn how the podocytes are damaged in disease and what we may be able to do to maintain or restore podocyte health and function. Professor Moin Saleem, the head of Bristol Renal, pioneered a technique to culture human podocyte cells in the laboratory, allowing us to closely study podocyte function. Cells, including the podocyte, constantly monitor their environment. This information is communicated to the nucleus of the cell via cell signalling pathways. We can study the activation of these pathways to get an idea of how the cell is ‘feeling’. We can then use drugs or other treatments to counteract these pathways.
When cells detect something that they’re not used to, they often respond in unusual and unhelpful ways. This is seen in the podocyte in response to the circulating factor. Fundamentally, we would like to find a treatment that can ‘tell’ the podocyte that everything is fine and it should put its tentacles out again and reform the final layer of the filtration barrier.
A lot of our work is funded by Kidney Research UK and the Nephrotic Syndrome Trust and is very disease focused. We have projects looking at each layer of the glomerular filtration barrier and how it is compromised in disease. There are people looking at the genetic components of nephrotic syndrome and using the latest sequencing and analysis to discover novel pathological gene variants – and we are heavily involved in coordinating several projects that seek to collect as much clinical information about nephrotic patients as possible.
Nephrotic syndrome is rare, however as a syndrome, the condition can be quite variable. Therefore, having a large resource of patient information is essential. We have many collaborations with industrial partners and other academics within the UK and across the world. We believe that our collaborative and interdisciplinary approach is the fastest route to a cure.