Imma Perfetto
Cosmos science journalist
An Australian researcher has been awarded $60,000 to build more complex models of the human lung, with the hope to discover new therapies for respiratory diseases.
Dr Rhiannon Werder, team leader at the Murdoch Children’s Research Institute (MCRI), was awarded the National Stem Cell Foundation of Australia’s 2024 Metcalf Prize for her work using stem cells and 3-dimensional ‘mini-lungs’ to create better models of genetic and acquired lung diseases and infections.
“Respiratory infections touch the lives of literally every person in the world, at least once per year,” Werder tells Cosmos. “This can span from the common cold … [to] very serious, life-threatening infections.
“In terms of chronic lung diseases … we’re really looking at genetic causes. We look at cystic fibrosis and we also look at a disease called alpha-1 antitrypsin deficiency, which has less PR than cystic fibrosis but … is the only known genetic cause of emphysema.”
Any cell type from a donor can be turned into a pluripotent stem cell, which can in turn be prompted to differentiate into any cell type of the body, including the specialised cells that make up the lung.
“The reason that [my team and I] use stem cells is because the respiratory conditions that we’re focusing on … uniquely affect humans,” says Werder.
“Therefore, in order to understand these diseases and to ultimately find cures, we need to use a model that mimics the human lung specifically.”
For years, Werder says she and others in her field have focused on the epithelial cells that line the lungs, which are the first line of defence against any microbes, pollutants, or toxins we breathe in.
But epithelial cells don’t work in isolation.
“Those cells are supported by many other cells that reside in our lungs, like immune cells and blood vessel cells and other structural support cells,” says Werder.
“Because all these cells work together, I think it’s vital that the mini lung tissues that we’re making from stem cells includes all those other cell types.”
The Metcalf Prize will help fund a project to examine the coordinated responses of complex mini lung tissues (lung organoids) to respiratory infections with human rhinovirus (which causes the common cold) and influenza virus.
The team will use a technique known as single-cell RNA sequencing to analyse the molecular signals in each individual cell.
This will allow them to understand the events happening as they’re infected.
“It will also allow us to look at how the neighbouring cells around that actively infected cell help [it] to clear the infection,” says Werder.
“What we want to look at is how the cells in the lung communicate effectively to clear infections, and potentially how that communication … goes awry and how that would then lead to severe disease.”
By better understanding this communication between cells, Werder hopes to identify pathways to target therapeutically, with the ultimate goal of developing “host directed therapies”.
“What this approach would involve is essentially harnessing our own immune system and our own immune defence to fight off these infections, rather than focusing on perhaps a more traditional approach, which is targeting the respiratory pathogen itself,” she explains.
These traditional therapies, such as antimicrobials, give the pathogen the opportunity to develop resistance. Augmenting the immune system’s ability to clear the infection itself would not.
More experiments are needed to identify exactly how that could be done, but Werder has a few ideas.
“We know what helps our body to clear a virus naturally. It’s a type of immune defence called antiviral immunity,” she says.
“What I would think we would do is come in at key points in that antiviral immune response and boost it. Maybe it would be adding in some of the key molecules that we know are important for initiating that defence.
“If we had, for instance, an inhaled therapy that would deliver that directly to our lungs. Maybe we’re just helping our immune system a little bit more, rather than relying on our own cells to be making all those effectors.”
Werder will be presented the Metcalf Prize next week at the Australasian Society for Stem Cell Research Annual Scientific Meeting in Adelaide, alongside Dr William Roman of the Australian Regenerative Medicine Institute at Monash University.
Roman is being recognised for his work growing human “mini-muscles” on a chip to understand how the skeletal muscle cell connects with neurons and tendons to create working muscles.
