Six of the best

A native bird, brain damage and protein “bombs” – these are just three of the SBS research topics that attracted Marsden Fund grants in November. The six winning projects are profiled below.




Preparing the hihi for a warmer world

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Dr Anna Santure

Dr Anna Santure and her collaborators Dr John Ewen and Dr Patricia Brekke at the Institute of Zoology in London won $808,000 for a study of the hihi, or stitchbird (Notiomystis cincta), a rare honeyeater endemic to the North Island and its adjacent offshore islands.

Dr Santure says that in the coming decades, a warmer, drier climate is likely to be unsuitable for hihi unless they can adapt. She says that predicting how populations adapt to environmental change requires knowledge of both the complex genetic basis of traits linked to survival and reproduction, and the selection pressures that are acting on the population.

Dr Santure will be using data from one of the best long-term population studies of an endangered wild bird population, the hihi population on Tiritiri Matangi, to understand the species’ potential to adapt. “The dataset of 1,500 individuals offers a rare opportunity to determine the genetic basis of traits important for survival and reproduction”.

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A female hihi. Picture by Patricia Brekke

Hihi possessing “high genetic value” will be targeted for breeding programmes and for the foundation of new populations. “The implications of the research are that by understanding the genetic basis of traits important for survival and reproduction, we’ll be able to predict the genetic value of individuals and implement this directly into conservation management decisions,” says Dr Santure. Genetic information will also be used to ensure variation in the population is maintained.

Dr Santure has been with SBS just a year, and says the Marsden Award is “absolutely fantastic” as it allows her to establish her own research programme in collaboration Dr Ewen and Dr Brekke, as well as fund both a PhD and postdoctoral position.

The project is called 'Predicting the adaptive potential of small populations: A case study in the endangered New Zealand hihi.'


Protecting the brain in oxygen loss

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Dr Anthony Hickey

Dr Anthony Hickey and Associate Professor Nigel Birch of SBS, Dr Neill Herbert of the Institute of Marine Science at Leigh and Associate Professor Gillian Renshaw of Griffith University in Australia won $773,000 for their study of hypoxic brain damage – injury caused by a lack of oxygen to the brain.

In adult humans, that’s a fast track to severe brain damage or death. However, says Dr Hickey, some animals can go for hours without oxygen, and in low temperatures, some vertebrates, such as turtles and crucian carp, can endure hypoxia for months.

Intertidal rock-pool fishes, he adds, show a remarkable capacity to routinely live with limited oxygen as temperatures rise, rock pools lose their oxygen with receding tides, and the fish suck up what oxygen is left.

To survive, says Dr Hickey, these creatures must be able to tolerate acidification of their brain and the cellular energy depletion that typically causes brain damage and death in other vertebrates. “So this is our main question: How do oxygen-starved rock-pool fish avoid brain damage? How do they cheat death?”

The study will test physiological, tissue and sub-cellular mechanisms that have evolved in New Zealand intertidal triple-fin fishes to protect oxygen-starved brains. “We hope to gain insights that may then provide insights into how we can protect mammalian brains in stroke and asphyxiation.”

The Marsden project is called 'Using a natural model to understand how to avoid hypoxic brain damage.'

Scrutinising marine toxins

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Distinguished Professor Margaret Brimble

Distinguished Professor Margaret Brimble, of SBS and the School of Chemical Sciences, won $765,000 to construct the molecular structure of a complex marine toxin called portimine in the laboratory. The compound was isolated in 2013 from algae collected in Northland.

“Portimine has an unusual chemical structure and interesting anticancer properties that we hope to investigate by correlating the structure with the biological activity,” says Professor Brimble. “The science of drug discovery is underpinned by the ability of chemists to create new molecules, so this project tests the boundaries of where the field of synthetic organic chemistry can take us.”

Professor Brimble is frank that without the Marsden fund, she’d be in a difficult situation. “The only agency I can apply to in order to pay for my fundamental research is the Marsden Fund. So winning a grant means I can keep doing my research and buy all the expensive specialist chemicals that need to be imported from overseas.”

The full title of her research is 'Unravelling the unprecedented architecture of the NZ natural product portimine using molecular chess.'


How genes and environment influence flowering

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Associate Professor Jo Putterill in a University rose garden

What are the gene-environment interactions in plants that lead to flowering? Associate Professor Jo Putterill, SBS Deputy Director (Research) is asking this question about the legume Medicago, a clover-like plant, in her $773,000 Marsden-funded research.

“We are hoping to find out how two signals, hours of daylight and low levels of nitrogen, stimulate flowering in the Medicago,” says Associate Professor Putterill, who will be working in SBS’s Flowering Lab with postdoctoral fellow Dr Mau Jaudal, PhD students Geoffrey Thomson and Chong Che, and research technician Lulu Zhang. “We hypothesise that these two cues promote flowering using overlapping mechanisms, but in a novel way compared to other plants.”

The team will be using genetics and what scientists informally call “omics” approaches – those derived from genomics, proteomics and metabolomics.

Associate Professor Putterill says that the timing of crop flowering is important to gain the best yields of seeds, grains and fruits, but also for aspects such as fodder quality and long-term survival. Flowering, in turn, impacts on plant-dependent organisms such as insects and birds.

The ultimate aim of the research is to provide plant breeders with the best tools possible, she says. “However, we are also really interested in plant genes and how they have evolved to control the timing of flowering in such diverse ways in different plants.”

The Marsden is a welcome boost: “It enables me and my research group to work on a fundamental question in biology and in food security. It’s also three years of funding that enables a talented group of people to work together and develop their careers.”

The official title of the project is 'Questioning the CO-FT regulon model and discovering genes that regulate photoperiodic and low nitrogen-induced flowering in the model legume Medicago.'


Protein ‘bombs’ – a new weapon?

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Dr Shaun Lott

Dr Shaun Lott and his team recently determined the three-dimensional structure, at an atomic level, of a protein that kills insect pests such as the New Zealand grass grub. This protein is produced by a soil bacterium that they discovered in a field in Canterbury.

The protein, Says Dr Lott, acts like a bomb: “It shields a toxic payload inside a shell before delivering it to specific cells in the insect's gut. We believe that this is the first known example of what may be a widely-used strategy in life for the delivery of proteins, and not just toxic ones, to specific locations.”

The protein was initially identified by Dr Mark Hurst at AgResearch Lincoln, and he’s an associate investigator on this $773,000 Marsden project. Their work on the insect toxin protein structure was published in top scientific journal Nature last year, and the plan now is to explore the structures and functions of related proteins in other biological systems, including the human nervous system.

“We hope that by understanding this mechanism of protein delivery, we can ultimately engineer the natural systems to produce better non-chemical insecticides, or even deliver peptides as human therapies,” says Dr Lott.

He is very grateful to have won a grant. “Without a Marsden grant, this work could not progress. We have well-funded competition in this area from a group in Germany – internationally, it’s a very competitive area of research.”

The project is called 'RHS-repeat-containing proteins: A new paradigm for targeted protein delivery.'

Exploring super-strong proteins

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Dr Paul Harris, Dr Paul Young, Professor Ted Baker and Dr Chris Squire

Dr Chris Squire, Professor Ted Baker, Dr Paul Harris and Dr Paul Young won $750,000 for a protein project. Proteins are the working molecules of life, performing many diverse and complex functions – as enzymes, messengers, transporters, and structural scaffolds among them.

Each protein is a long chain of amino acids – a polypeptide chain – which must then fold up to a particular shape on which the function of the protein depends, says Dr Squire. If the protein does not fold correctly, it will not have the correct shape to be able to perform its function. The result? Disease.

The folding process is guided by very weak forces between the side chains of the amino acids in the polypeptide chain. Dr Squire, who is the project’s co-principal investigator with Professor Baker, says that although these side chains display a variety of chemical groups, evolution seems to have selected a process in which they do not form cross-links, or covalent bonds, with each other. This is to avoid mistakes being made during folding and the protein being stuck with an incorrect shape.

The Squire-Baker team has recently discovered two different and unusual kinds of cross-links inside elongated proteins found on the outside of bacteria. These unusual bonds between amino acid side chains greatly strengthen the proteins, which might otherwise be ripped apart in the harsh environment that bacteria experience.

The team aims to understand why these unusual bonds form, under what circumstances they form, and how widespread these types of cross-links are. “Can we find them outside the limited number of bacterial species we currently know have them?” asks Dr Squire. “Can we perhaps find even more bizarre and unusual cross-links, for example, in the bacteria that grow at high temperature and pressure, such as those found near underwater volcanic vents?”

The research, he says, will help science understand fundamental properties of proteins, why they are stable, and why, under certain conditions, they can selectively form chemical bonds that would destroy the protein’s function if formed indiscriminately.

“We hope to better understand how proteins on the surfaces of bacteria, which are subjected to extreme environmental conditions, can withstand extreme stress and allow bacteria to be some of the most resilient organisms on the planet,” says Dr Squire.

“We suspect that there is much more out there to be discovered and understood and that this work will not only change how we understand such a fundamental process as protein folding, but also open up applications in biotechnology. We may, for example, be able to engineer artificial proteins with enhanced stability – super-stable proteins – for industrial applications.”

The Marsden grant allows the team to continue what has already been world-leading work, says Dr Squire. “It allows us to continue this ground-breaking research, to capitalise on the methods we have developed for discovery, and to fully exploit what we now understand.

“Most importantly, the opportunity to make discoveries such as these is intensely exciting for all involved. It’s a great chance for graduate students and other emerging researchers to experience the excitement of scientific discovery.”

The Marsden project is called 'Probing the chemistry of novel protein crosslinks.'