Breaking the mould

While she’s not a fan of mould at home, Dr Rose McLellan finds it endlessly fascinating in the lab.

Dr Rose McLellan

Rose began her life in academia with an undergraduate degree in Biotechnology and Chemistry. When considering her options for postgraduate study, she honed in on an often-overlooked subject: mould.

“If you grow it in different environments, it grows completely differently to what you would expect.

“When it’s stationary, it grows like the mould you’d see on bread. But if you take those spores and put them in a shaking liquid culture, it grows these little balls called mycelia.”

Now a Post-doctoral Research Fellow at Te Kāuru—Ferrier Research Institute, Rose is continuing to develop her interest—and investigate the biosynthesis of potentially lifesaving, or life-changing, compounds found in mould.

Originally from the Kāpiti Coast, Rose was attracted to Te Herenga Waka—Victoria University of Wellington because of the chemistry programme. After being awarded a $5000 Wellington Tangiwai (School leaver) Scholarship, and then completing her undergraduate degree, she was inspired to move into postgraduate study by Professor Emily Parker. Professor Parker’s research group focuses on the development of new treatments for diseases, and using natural biosynthetic machinery to efficiently generate valuable products. Professor Parker, Dr Rosannah Cameron, and Dr Matthew Nicholson, a senior commercialization manager at Wellington UniVentures, became Rose’s PhD supervisors, and her research recently placed her on the doctoral Dean's List—a commendation acknowledging exceptional research, only awarded to a handful of PhD graduates each year.

Rose’s research employed state-of-the-art synthetic biology techniques to interrogate and reconstruct fungal biosynthetic pathways to create cellular factories to efficiently produce high-value natural products with potential use as therapeutic agents. This has been a challenge in the past because of the structural complexity of bioactive fungal metabolites, and their low abundance in nature. Her ongoing research explores the biosynthesis of these metabolites using mould as a biotech tool.

"Mould is so much more than an unwelcome houseguest," Rose explains. “When harnessed correctly, it can be used to grow incredible things.”

While you might not be excited to find mould in your home, or on your bread, it can be extremely beneficial in a scientific context—with certain compounds found within mould potentially holding the key to treatments for a whole range of conditions.

“It's the compounds in mould that we want to access, we want to understand how they're made by the fungus. A large proportion of fungi don't make these compounds in high yields, so what we do is look at their genomes.

“We sequence their genomes or access them online—other people may have already sequenced it and we can access that information.

“We look for genes that are similar to things we already know, and we basically express those in a different fungus that's efficient at making the type of compounds we want to make. By doing that we can understand how these compounds are made, reveal biosynthetic pathways, and hopefully bring these potential therapeutics to the market.”

The potential applications of Rose’s research are expansive and remarkable. Figuring out how to make certain compounds is important, given they can potentially provide useful bioactivities such as anti-insect activity (with potential uses in flea treatments for animals, for example), anti-cancer activity, and anti-viral activity.

“This class of compounds has an incredibly diverse range of potential applications—but to use them, we need to figure out how to make them more efficiently. That's one of the great things about using synthetic biology as a tool, we can find out how to make these super exciting natural products."

Te Kāuru—Ferrier Research Institute is co-located with Callaghan Innovation in Gracefield and works closely with them to upscale processes such as the fermentation of fungi and work towards commercialisation, as well as others including AgResearch and the University of Otago.

Rose began her two-year postdoctoral position at the Institute in January 2022.

“I was on holiday when I applied for the role, and I found out that I got it not long after that—it was just before I was about to go skydiving, and I thought ‘this is a great way to celebrate getting a job!’”

She’s really enjoying her time at the Institute, and says her colleagues are both inspiring and supportive—pointing her in the right direction but also encouraging her to explore her own ideas as well.

“There is freedom but direction at the same time.”

Professor Gary Evans, Director of Te Kauru—Ferrier Research Institute, praises Rose’s research, and says it highlights the value of the chemical and synthetic biology team’s work.

“As one of the Institute’s leading scientists, Professor Parker knows the importance of understanding the molecular-level chemical knowledge that underpins biology. She—along with clever and creative early career researchers like Rose—has explored how to use that biology to do exciting new chemistry.

“The types of revolutionary approaches developed by this team will help transform Aotearoa into a high-wage low-emissions economy, with brilliant early career researchers like Rose at the crest of this knowledge wave.”