EMBL Australia group leader Dr William Roman – based at the Australian Regenerative Medicine Institute at Monash University – is one of two winners of the 2024 Metcalf Prizes for Stem Cell Research for his work that involves growing human muscles on a chip to better understand intracellular communication.
Dr Roman is using the ‘mini muscles’ as a model to understand how the skeletal muscle cell, the largest cell in a human body, connects with neurons and tendons to create working muscles, with the hopes that this work will enable researchers to better mimic organs outside the body.
He is also studying what happens when communication between neurons and muscle cells breaks down as we age, and in degenerative diseases such as motor neuron disease (MND).
This research will lead to stem cell technologies for disease modelling, drug screening, cellular agriculture & biorobotics.
The prestigious $60,000 prizes will be formally awarded by the National Stem Cell Foundation of Australia (NSCFA) to two winners – Dr Roman and Dr Rhiannon Werder – next week at the Australasian Society of Stem Cell Research Annual Scientific Meeting in Adelaide.
good communication between cells is key
Dr Roman says: “Researchers around the world are mimicking organs, growing mini- kidneys, mini-hearts, even mini-brains. However, a key challenge with these organ-on-chip models is that different cell types do not naturally interact to form the mature connections seen in real organs. We first need a deep understanding of how stem cells communicate in space and time during development.”
His focus is on skeletal muscle cells, also known as muscle fibres. They are two to three centimetres long, which makes them easier to work with.
Following his PhD, he founded and led MyoChip, a multinational project to build a muscle on a chip.
Now he plans to go further and persuade the muscle fibres to connect with tendons, forming a complex structure, known as a myotendinous junction, that transmits force from our muscles to our tendons.
“We can already put two cells next to each other in a dish, but it doesn’t seem like they’re interacting the way they should,” Dr Roman says.
“So, what we’re trying to understand is how good relationships naturally form. And then we want to reproduce that in a dish, providing the right factors or ambience, for two cells to want to interact, at the right time and place in their development process, to form stable, long-term relationships.”
To achieve this, his team is first focused on understanding the cross-talk between cells – aka “good communication” – which contributes to stable relationships in the development of a healthy myotendinous junction.
“This approach will serve as proof of concept to determine if mapping intercellular communication can be used for tissue engineering,” he says.
“And, if we can do that in muscles, it can then be applied to engineer next-generation organ-on-chip systems, using a controlled, bottom-up approach akin to building cars – starting from scratch and piecing together all the different components to recreate organs.”
Then he hopes to teach his ‘muscles’ to connect with neurons to form a neuromuscular junction, in which a neuron forms synaptic connections with a muscle cell. And that would transform research into debilitating muscular and neuromuscular disorders – including MND in which people lose control over skeletal muscles that allow them to move, talk, eat and, ultimately, breathe.
“Modelling a neuromuscular junction will allow us to tackle neuromuscular diseases that are poorly understood and for which there’s no cure,” Dr Roman says.
“We’re still trying to form a mature neuromuscular junction that better mimics what happens in our bodies. Right now, nobody has been able to do this in a dish.”
2024 Metcalf Prizes to be awarded next week
The Metcalf Prize for Stem Cell Research recognises exceptional mid-career stem cell researchers in Australia and is presented to one female and one male researcher each year.
The other prize winner – Dr Werder, a team leader at the Murdoch Children’s Research Institute – grows mini lungs in a dish that mimic the complexity and function of lungs in living people to better investigate respiratory infections and drive new treatment discoveries.
“Rhiannon and William’s work illustrate the power of stem cells to create living, functioning 3D models of healthy and diseased human tissues and organs, from mini-lungs to mini-muscles,” says Dr Graeme Blackman AO, the chairman of the Foundation.
The awards are named for the late Professor Donald Metcalf AC who, over a 50-year career, helped transform cancer treatment and transplantation medicine, paving the way for potential stem cell therapy in the treatment of many other conditions.
The NSCFA is an ATO-registered, tax-deductible health promotion charity dedicated to promoting the study and responsible use of stem cells to reduce the burden of disease.
See more at: www.stemcellfoundation.net.au