Dr Rhiannon Werder is growing ‘mini-lungs in a dish’ that mimic the complexity and function of lungs in living people.
The Team Leader at Murdoch Children’s Research Institute (MCRI) has already used stem cell-derived lung cells to create models of human genetic diseases, like cystic fibrosis, and acquired lung diseases and infections, such as the common cold.
Now she plans to grow 3 dimensional models of human lung tissue, or ‘mini-lungs’, in a dish to better investigate respiratory infections and drive new treatment discoveries.
In recognition of her leadership in stem cell research, she has received one of two annual $60,000 Metcalf Prizes from the National Stem Cell Foundation of Australia.
Lung diseases and respiratory infections rank among the top causes of morbidity and mortality in children globally.
“Every time we breathe in, we breathe in potentially horrible things, meaning our lungs are under constant attack – so, it’s no wonder things go wrong,” says Rhiannon matter-of-factly.
“Epithelial cells that line the lungs are our first line of defence, and the first cells that anything we breath in interacts with,” Rhiannon says. “It’s incredible that these cells that line our lungs are so well equipped – attacks are happening almost with every breath, and most of the time you don’t even know about it, because the epithelial cells just deal with it.
“But, of course, underneath those cells are many other cell types, and to better understand respiratory diseases, we need to persuade these other cells to grow in our models of human lung tissues, or ‘mini-lungs’.
“We’ve already had really nice success incorporating immune cells, and what we’re working towards is making mini-lungs in a dish that have full complexity of the lung so that we can study respiratory infections, including how they impact children with chronic lung diseases.
Rhiannon wants her work to lead to treatments that help children breathe easier. Her focus is on how we can teach the lung cells and the immune system to deal with invaders more effectively. This ‘host directed therapy’ contrasts with traditional disease directed therapies that target specific bacteria or viruses, which can then become resistant to treatment.
“We want to find therapeutics to harness the host immune system to treat and/or prevent respiratory viral infections in vulnerable children with chronic lung disease all the way through to anyone who might get a cold every year.”
She’s investigating a range of respiratory infections, from the common cold (rhinovirus) to Group A streptococcus and Mycobacterium abscessus, in tandem with observing how people with genetic lung diseases, like cystic fibrosis and Alpha-1 antitrypsin deficiency, deal with respiratory viruses.
By growing her models of lung tissue using stem cells from health donors and from patients at the Royal Children’s Hospital in Melbourne, she can start to understand what’s going wrong in both genetic disease and during infections.
“What’s also amazing to me is that when the respiratory system does get overwhelmed, and you have an infection, all the cells come in to help the epithelial cells get rid of whatever it is, and then repair themselves.
“It’s just the most beautiful, coordinated response between local immune cells, recruited immune cells and other structural cells that sit really close to the epithelial cells.
“Each phase of that response is very different and coordinated, and when things don’t go right in that response, that’s when we end up with potentially life-threatening disease.”
Rhiannon says the Metcalf Prize will help her start to address the ‘big question’ of how this diverse range of cells communicate following infection.
For her, the potential power of stem cells is the flexibility to use them at scale, for example in major drug screens, or to genetically manipulate them to find better therapeutics.
“Finding new therapeutics in the lung space has been very slow – and probably a big reason behind this is we’ve been using the wrong model for a really long time.
“Many of the diseases that we’re studying, which affect the lungs, are very human specific diseases, and mice don’t get them.”
Rhiannon received a PhD in Immunology from the University of Queensland, in 2017, uncovering novel antiviral mediators regulating responses to respiratory viral infections. She was then awarded a NHMRC CJ Martin Early Career Fellowship and an Australian Government Endeavour Research Fellowship to undertake post-doctoral work at Boston University’s Centre for Regenerative Medicine. At the height of the COVID-19 pandemic, her research led to significant findings, including the first discovery of how the lung epithelium responds to the SARS-CoV-2 virus. She joined Murdoch Children’s Research Institute in October 2022.
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