This year’s Marsden funding awarded to the Otago Department of Biochemistry shows again the importance of understanding fundamental molecular details for solving big challenges, in this case within medicine and agriculture.
Dr Sarah Inwood and Professor Sally McCormick lead research teams working on the two successful projects: how a virus affects a biocontrol parasitoid wasp that predates troublesome weevils, and how an antidepressant drug might help lower cholesterol levels in blood. Read more about these projects below.
The Marsden Fund grants are administered by the Royal Society Te Apārangi on behalf of the Marsden Fund Council, and come from a contestable fund that supports investigator-led fundamental research in New Zealand. The grants are highly competitive, with success rates around 10%.
Both Sarah and Sally happen to come from near the same small town on the Canterbury Plains (Southbridge), so there must be some amazing early science education happening in that area.
Ka mau te wehi! Koia kei a kōrua. Amazing! You two are awesome.
Dr Sarah Inwood: Using recent genomic advances to investigate why biocontrol using parastitic wasps is declining over time
Working with: Professor Peter Dearden (Otago Biochemistry)
Dr Sarah Inwood flanked by images of the South American parasitoid wasp Microctonus hyperodae - emerging as a larva from an Argentine stem weevil (left) and the adult wasp (right).
When you have a pest bug wrecking havoc in farms all over the country, and you don’t want the danger or expense of using pesticides to keep them under control, what do you do? You can introduce a natural predator of the bug, an option known as biocontrol.
The Argentine stem weevil devours a variety of crop plants, particularly perennial ryegrass, and is therefore one of the most significant insect pests in the pastoralist, grass-reliant country that is New Zealand.
The South American parasitoid wasp Microctonus hyperodae happens to feed on the weevil in a, frankly, horrifying manner. The wasp attacks an adult weevil with its sting, then lays its eggs directly into the weevil’s body cavity using its needle-like ovipositor. As the wasp egg develops into a larva and eats the weevil from the inside, the host weevil manages to live on. It only dies when the wasp larva bursts out of the weevil’s body, ready to pupate, before finally becoming an adult wasp.
New Zealand took advantage of the wasp’s unsettling but effective ability to keep weevil numbers down back in 1991, when farmers started introducing it to the country’s pastures.
Initially the parasitoid wasp biocontrol strategy was a great success, reducing pasture damage caused by the weevil, and parasitism rates observed in weevils were as high as 90%. Since then, however, parasitism rates have dropped significantly.
So what do you do when your biocontrol agent stops working? You use your molecular tools to investigate.
On the back of a recent study into the transcriptome of the parasitic wasps, Dr Sarah Inwood’s research team discovered a new virus that infects the wasps and may have caused the loss of pest control. There is increasing evidence generally that viruses influence efficacy of biocontrol agents such as these parasitic wasps.
Sarah’s team have an exciting opportunity to look into this virus and the effects it has by reconstructing the spread of the virus between wasp populations and to Argentine stem weevils during parasitism and working out how it affects wasp behaviour.
Through collaborators at AgResearch, the team has access to an historical collection of wasp samples taken during nearly ten years while they were mass-reared in containment during the 1990s, along with wasp samples taken from the field soon after release. These samples will allow the team to investigate the infection dynamics of the virus. The team will also use living wasps to determine what effects the virus has on wasp behaviour and fitness.
Sarah’s enthusiasm for her research project is palpable. “The experiments that will be funded by this Marsden Fast-Start are ones that I have been dreaming up for a few years now, following on from a tangent I started down during my PhD. It is amazing to have had a research direction that I’ve brought together myself be recognised by a prestigious funding source like Marsden!”
Professor Sally McCormick: Unravelling the connection between serotonin and Lp(a) catabolism
Working with: Dr Gregory Redpath (co-principal investigator) of the University of New South Wales, and Otago biochemist and postdoctoral fellow Dr Katie Peppercorn
Professor Sally McCormick alongside representations of the molecules she is investigating, including serotonin and its receptor, Lp(a) and its receptor, and a pinocytotic vesicle.
Professor Sally McCormick has has based her research career on studying the link between heart disease and the molecules that carry fats and cholesterol around the body. So it is surprising to see her name associated with research into antidepressants.
What has depression got to do with heart disease? Isn’t one in the head and the other in the chest?
The answer lies in the infinite complexity of how the body works at the molecular level (a topic dear to every biochemist’s heart) and the sometimes surprising, unpredictable ways that drugs can interact with the body.
Often medications have additional effects on our body.
Researchers in the McCormick lab have recently discovered that certain antidepressants increase the liver's ability to remove "bad" cholesterol linked to heart disease.
This bad cholesterol is called “Lp(a)” and is a tiny package that travels around in the blood, made up of low-density lipoprotein with an additional protein called apo(a) attached. People with high levels of Lp(a) in their blood are much more likely to have heart disease.
Sally’s team found a new way that the body clears Lp(a) out of the blood that involves plasminogen receptors on liver cells. What is especially interesting is that this way of clearing Lp(a) out of the blood is increased by serotonin-based antidepressants.
Her team will now investigate how antidepressants can change cholesterol levels in our blood. They will decipher the mechanism underlying this, and look for further evidence of it happening in animal models and in a large database of human data from the UK.
As well as uncovering fundamental new knowledge on how serotonin signalling affects blood cholesterol levels, the research could lead to more targeted therapies that could reduce the risk of depression and heart disease.
Sally emphasises the many potential outcomes that could come from this project. “It could identify new therapeutic targets to lower Lp(a), support the repurposing of certain antidepressants towards Lp(a)-lowering, and may lead to the tailoring of antidepressant treatments to reduce the risk of heart disease”.
Find out more about Sarah and Sally’s research here: