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Michelle Colgrave: Protein Detective

Michelle Colgrave

In the brain, some proteins determine when animals reproduce. In foods, others determine whether a coeliac will have a bad reaction. Professor Michelle Colgrave is sorting out the goodies from the baddies.

Picture Michelle Colgrave, working in her laboratory at Australia’s national science agency CSIRO in Australia, as a sort of heroic forensic detective. Instead of fingerprinting or examining stab wounds of human subjects, she uses a technique called mass spectrometry to investigate proteins, identifying their roles in various situations – be it beneficial or sinister.

“What we’re trying to understand is what are the proteins in any given system and how do they interact, and what can we infer about the biology of a system through knowing what those proteins are,” she says. “Proteomics is the study of proteins using mass spectrometry. It’s essentially capturing a snapshot of any cell tissue or organism at a point in time.” The technique is highly transferable, Colgrave says. “I do everything from measuring peptides involved in abalone spawning through to defining grain quality or safety by applying the tools we have to these very different challenges.”

Colgrave has earned multiple awards for this work, including in 2020 the ICM Agrifood Award from the Australian Academy of Technology and Engineering. In addition to her role as future protein lead in CSIRO Agriculture and Food, she has been appointed chief investigator in the new Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science. There, 26 organisations work together, with a co-investment of $89 million to spend over the next seven years.

It all started for her with an inspiring science teacher, Mr Bruce, at her high school in Batemans Bay, NSW. “He was just a really great teacher,” Colgrave says. “From there, I went to an agricultural high school in Sydney for my last two years of school, so that’s where the merge of agriculture and science came into play.” Colgrave studied science at Wollongong University, mentored and inspired by Professor Margaret Sheil, Australia’s first female professor of chemistry. She ended up completing a PhD on bioanalytical mass spectrometry under Professor Sheil’s supervision.

Colgrave says many other researchers use proteomics to understand human health, but she has focused on agriculture and food.

“We’ve applied it to agriculture in the sense of ‘can we make a plant that produces something that’s going to be beneficial?’ An example is we’ve made a canola variety, through genetic modification (GM), that produces omega 3 oils.” These oils have many benefits to human health, including for heart and brain development, but have traditionally been harvested from plankton-eating fish.

If we’re going to harvest all of that fish oil from the ocean, then that’s going to decimate our oceans,” Colgrave says. “We’re providing the same nutrition, but doing it in a more sustainable way, because for every 10,000kg of fish that need to be harvested, we can grow a hectare of this canola. My role was to use proteomics to show that when you’ve got a genetically modified organism, that it’s going to be safe for consumption and also safe for the environment.”

Colgrave has also researched gluten, in particular determining what is safe for coeliacs and those with gluten intolerance to eat. “It could be the gluten itself, or it could be the other proteins that exist in the gluten-containing grains that are interfering with your metabolism,” she says. Her research helped the CSIRO develop an ultra-low gluten barley variety called Kebari. “Farmers with a grain like Kebari can grow that for a premium price because it’s addressing this niche market,” she says. “In terms of consumers, it’s more about ensuring that the food that they’re eating is safe. They can have some confidence that when they see a ‘gluten-free’ label on a packet, they’re not actually going to be sick. And that can happen at the moment.”

Colgrave finds it easy to explain why some plant proteins make some people sick. “Plants can’t run away. So what do they do? They make all these defence molecules to make insects feel a bit sick when they eat them. We then go and make products out of them. So it’s not surprising that sometimes, we get sick or experience these gastrointestinal complaints just like the insects!”

Her work in understanding proteins can also be applied to animals. “When we’re talking about reproduction, whether it be in cattle in northern Australia or whether we’re looking at abalone, there are neuropeptides in the brain that are released under certain conditions that trigger that response. So if we understand what those peptides are, we can potentially intervene to ensure a more sustainable and reliable production system. For example, on abalone farms, spawning has always been a bit of an issue because the abalone are not getting the same cues they would in the environment – whether it’s the moon and the tides, whether it’s algae in the water, or other factors that come into play.”

Lately, Colgrave has been working on understanding proteins that could help with many people’s changing dietary patterns. “For example, we’re seeing what we call the rise of the ‘flexitarian’ – those who are starting to reduce their red meat intake and perhaps they’re increasing their plant protein intake. So we’re doing a lot of work around that and understanding what are the next plant proteins that they could use, such as pulses like lupin, and understanding their nutritional value.” This also includes looking at insect protein sources such as black soldier flies and crickets. “The part that I play in this is understanding with these insects whether they will also have anti-nutritional proteins that will cause food allergies.”

Colgrave says that at times GM technologies have received bad publicity, but the way she sees it, they can be considered as safe as conventional breeding programs. “I can cross two different varieties of wheat to produce a new variety. As long as I’ve just crossed them, then that’s not GM and there’s no requirement for safety assessment. On the other hand, the requirements are extensive for GM products to prove safety from both environmental and health perspectives, so you could argue that they’re even safer.”

I don’t think that genetic modification is bad. What we have to understand is when we make a change, what else are we changing, and can we understand the effect of those changes?”

For the moment, it looks safe to leave these sorts of investigations in the hands of our protein detective.

Follow Michelle Colgrave on Twitter

Article by Ken Eastwood
Photo supplied

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