Dr Platt trained at the University’s Medical School after gaining an honours degree in Molecular and Cellular Pathology. She specialises in paediatrics and works in the renal department at Bristol Royal Hospital for Children. The scheme offered her a chance to further her understanding of the molecular and cellular basis of kidney disease in children, before training in her chosen sub-specialty of paediatric nephrology.
The podocyte is a highly specialised epithelial cell that forms an integral part of the kidney’s filtration barrier. The ability of the podocyte to respond to insulin is important for its health and survival, and therefore health and survival of the kidney itself. This is controlled by PPAR-γ (peroxisome proliferator activating receptor), which switches on the genes for the insulin signaling pathways within the podocyte.
Damage to the podocyte in people with type 2 diabetes is the first step towards the development of diabetic kidney disease. The glitazones protect the podocyte, and therefore kidney function, by activating PPAR-γ.
‘I wanted to investigate the role of PPAR-γ, its influence on how insulin works in the podocyte, and how its activation can prevent progression in diabetic kidney disease,’ says Dr Platt. ‘I saw this as a way to allow me to contribute to published scientific literature in my chosen field.’
The six-month scheme offered her the opportunity to work with Professor Richard Coward’s research team at the Academic Renal Unit in Bristol’s School of Clinical Sciences.
Dr Platt began by researching the literature and shadowing scientists to learn laboratory techniques useful for the project. Then she learned how to grow podocytes using mouse and human cell cultures, including techniques for making the podocytes insulin-resistant and a range of methods for studying them.
Finally, she researched the effect of different experimental conditions on low-passage (dysfunctional) mouse podocytes, including the effect of a glitazone called Rosiglitazone on how insulin works in the podocyte. This included studying pathways and proteins linked to the integrity of the kidney filtration barrier to better understand how PPAR-γ functions.
Her research showed that the glitazones activate well-established PPAR-γ responsive genes in podocytes grown in culture, and also protect podocytes from damage (induced by a toxin called PAN). Further investigation of the influence of the glitazones on the protein make-up of the cell revealed some interesting avenues to explore. These included protein networks involved in the motility and structure of the cell, and proteins for important cell survival and growth-promoting functions.
The next step is to test out on mice what happens when the PPAR-γ has been selectively ‘knocked out’ of the podocyte. Ultimately the aim is to show that when diabetes is induced in this mouse, the resultant kidney disease is significantly worse than in a mouse where podocyte PPAR-γ is present.
Dr Platt has presented her initial research internationally at the 48th European Society of Paediatric Nephrology Meeting in Brussels (P-213 Pediatr Nephrol DOI 10.1007/s00467-015-3158-7).
She has also published a review article in the journal Nephrology Dialysis Transplantation [1], the official publication of the European Dialysis and Transplant Association - European Renal Association.