From little things – The world-leading stem cell biology to rebuild a kidney

As soon as the scientists looked into the dish, they knew that it was a Eureka moment. Structures that had developed were recognisable – potentially, at least – as a human kidney forming. For the lead researcher, Professor Melissa Little, it was a career-defining moment; for the one in three Australians at increased risk of kidney disease, it was a moment of hope.

Professor Melissa Little

“It was the structure of the cells and the cell type present that allowed us to go, ‘Oh, wow! OK, now I think we might be getting there’,” she recalls.

The journey had begun more than a decade earlier when Professor Little started wondering if it might be possible to regenerate or recreate a kidney. Stem cell biology has revolutionised the world of science, making the impossible potentially possible.

“Now I can take a skin biopsy from a child who has presented with end-stage renal failure,  or even an adult, to make a stem cell and rebuild a model of their kidney in the lab,”  she explains. “It’s quite extraordinary.”

The research gains in the past three years have been equally extraordinary. Professor Little and her team in Melbourne at the Murdoch Children’s Research Institute have collaborated with researchers in Holland to successfully transfer a mini-kidney grown in a lab into a living mouse. The ability to make kidney tissue from human stem cells and have it develop into mature kidney tissue after transplantation has been hailed a significant breakthrough in the search for new ways to treat kidney disease.

The urgency to do so cannot be understated. Every day, 53 Australians die from end-stage renal failure. The disease is growing by 6 per cent a year and, by 2020, it’s predicted that one in 20 people will suffer from chronic kidney disease. Driven largely by obesity and diabetes, the annual cost to the taxpayer is a staggering $1 billion.

At present, patients are treated either with transplantation or dialysis. Only one in four patients with renal failure will receive a transplant and that is expected to blow out to one in five, or even one in six, as more and more Australians are diagnosed. Dialysis is expensive, difficult to live with, and is associated with high levels of morbidity and mortality.

“We’ve got a massive, growing disaster in terms of treatment of chronic kidney disease,” warns Professor Little. “We have to find some alternative that’s better than dialysis.”

The possibilities are enormous.

“If we model a disease, can we find a treatment? Can we actually use these models of a tissue to screen drugs that might treat the patient? Can we model for toxicity? Can we take drugs during development and say, ‘Let’s put it on a model of a human kidney and tell quickly and early whether or not it’s going to be a problem when you reach clinical trial’. If that’s the case, we can actually short-circuit the drug development pipeline and probably save a lot of money.

“Can we build a tissue that can be transplanted? Can we take kidney cells and put them back in and see if they’ll fix up the damaged kidney? We’re trying to work through all these options and see where they lead us. There’s a long way to go before we have anything that would be of value for clinical trials.

“And that’s the challenge. Now that the stuff we’re generating is public knowledge, there is a huge patient base that is very anxious to see treatment. All I can say is that, at the moment, I can only give you hope because I don’t have a cure.”

The questions keep her awake at night, as do the nightmares around keeping her staff employed and finding enough funding for the work. It’s not where she had ever imagined she would be at the age of 54.

“I’ve lived my career on fellowships that run for three to five years at a time, so you’re constantly trying to beg not just for your own salary but for the salary of all the staff.”

When she finished school, Professor Little had considered studying medicine but, not completely sure of what she wanted to do, enrolled in science with a major in physiology at the University of Queensland. She thought she would become a zoologist.

But an entire future was being shaped by her studies. She did her honours degree on the kidney and its regulation of blood pressure. Her PhD was on kidney cancer in children and, while on a Royal Society Endeavour Fellowship at the Medical Research Council Human Genetics Unit in Edinburgh, Scotland, she worked on kidney development.

Professor Little spent 23 years working at the Institute for Molecular Bioscience at the University of Queensland where her research work focused on the molecular basis of kidney development, renal disease and repair. She moved to Melbourne three years ago to become the Theme Director of Cell Biology and Head of the Kidney Research Laboratory at the Murdoch Children’s Research Institute. She is a Professor in the Faculty of Medicine, Dentistry and Health Sciences at the University of Melbourne, and Program Leader of Stem Cells Australia.

Professor Little has earned an international reputation for her work on the systems of biology of kidney development and also for her pioneering studies into potential regenerative therapies in the kidney.

“I’ve always done science internationally,” she explains. Since publishing the research protocol that has since become a blueprint for many research scientists around the globe, she’s widely acknowledged as a leader in the field. She’s the only researcher on the ‘Rebuilding a Kidney’ consortium who is not based in the US; the consortium is funded by the National Institutes of Health, the biggest biomedical research agency in the world, based just outside Washington DC.

Her global standing was instrumental in attracting almost 4000 leading stem cell scientists to the annual meeting of the International Society for Stem Cell Research in Melbourne in June.

Professor Little shares her success with a supportive husband, Mahlon, and their two grown children, Celeste and Nathaniel. “If people ask me to describe myself, I tell them that I’m a mum, a working mother with two kids I love, who has a passion for doing science and who has been enormously privileged. I think it’s fantastic being a scientist.

“One of the benefits of not having two scientists in a marriage is that he had greater job security and was willing to let me be passionate about my research. One of the things I say to young women in research is to choose your partner well!”