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Innovative Otago research supported by prestigious Marsden funding

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Thursday, 5 November 2015 2:15pm

Ted Ruffman father and son image
Psychology Professor Ted Ruffman’s father and son, Ken Ruffman and Charlie Ruffman. Professor Ruffman has been awarded a Marsden grant to study theory of mind in babies.

More than $11.7M in new government funding has been awarded to University of Otago researchers to undertake 20 world-class research projects pushing the boundaries of knowledge in their fields.

Their innovative projects are being supported through the Royal Society of New Zealand-administered Marsden Fund, which is regarded as a hallmark of excellence that allows the country’s best researchers to explore their ideas and showcase them internationally.

Researchers from across the University will lead the new projects, which include 13 standard projects and seven ‘Fast-Starts’ designed to support outstanding early-career researchers.

Deputy Vice-Chancellor (Research & Enterprise) Professor Richard Blaikie warmly congratulated the Otago recipients on their success in the prestigious funding round.

“The Marsden Fund is extremely competitive and is designed to encourage work of the highest quality on topics of great value. I am delighted that the excellence of our researchers’ proposals has been recognised and their world-leading studies supported,” Professor Blaikie says.

Professor Blaikie noted that Otago’s Vice-Chancellor Professor Harlene Hayne was among this year’s recipients, becoming the first head of a New Zealand university to be awarded a Marsden grant while in that role.

“At Otago, one of our defining characteristics is that the Vice-Chancellor and other members of the senior academic leadership continue as active researchers and teachers. This reflects the University’s deep commitment to maintaining a vibrant academic culture at all levels,” he says.

Professor Hayne, a Department of Psychology researcher, will lead a team evaluating interview procedures used to obtain children’s testimony. In a series of empirical studies, they will test the effect of these procedures on the content and accuracy of children’s reports and on jurors’ decisions.

Nationally, a total of 92 research projects were allocated $53.54 million (excl. GST) of funding this year. Only 7.7 per cent of the 1201 preliminary proposals put forward were ultimately funded.

The Otago researchers will pursue investigations at the forefront of disciplines that include anatomy, anthropology and archaeology, bioethics, chemistry, mathematics and statistics, microbiology, pathology, pharmacy, physics, physiology, psychology, religion, and zoology.

Their projects range from unravelling antiseptic resistance mechanisms in a bacterium commonly found in hospitals to studying how, and why, several new Buddhist monastic groups that preach messages of hatred and intolerance against religious minorities have emerged in South Asia.

Professor Blaikie says the wide span of topics being addressed by the Otago recipients reflects the breadth and depth of Otago’s research effort.

“I am particularly proud of the stellar performance of our early-career researchers, who were awarded nearly one quarter of all the ‘Fast-Start’ grants offered in this year’s round,” he says.

For more information, contact:

Professor Richard Blaikie
Deputy Vice-Chancellor (Research & Enterprise)
University of Otago
Tel 64 3 479 8513
Email dvc.research@otago.ac.nz

Otago’s Marsden Projects:

  • The ethics of research on clinical data and tissue without explicit patient consent
    Dr Angela Ballantyne (Primary Health Care & General Practice, University of Otago, Wellington) Fast-Start $300,000
  • Identifying novel DNA replication components through harnessing the resource of Mendelian disease
    Dr Louise Bicknell (Pathology) $840,000
  • A dilute supersolid of polar molecules
    Professor Blair Blakie (Physics) $790,000
  • The origins of social inequality in Southeast Asia: an exploration of health and wealth disparity at the emergence of state level society
    Associate Professor Hallie Buckley (Anatomy) $767,000
    Co-Principal Investigator: Professor Charles Higham (Anthropology & Archaeology)
  • Smoothing and inference for point process data with applications to epidemiology
    Dr Tilman Davies (Mathematics & Statistics) Fast-Start $300,000
  • Meet the neighbours: evidence for interaction between Lapita colonists and Papuan communities in Papua New Guinea
    Dr Anne Ford (Anthropology & Archaeology) Fast-Start $300,000
  • Shear force dependent regulation of epithelial Na+ channel (ENaC) and its relevance for blood pressure regulation
    Dr Martin Fronius (Physiology) $755,000
  • Targeted, triggered and zero waste prodrug activation
    Dr Allan Gamble (Pharmacy) Fast-Start $300,000
  • Out of the mouths of babes: Interviewing children in forensic context
    Professor Harlene Hayne (Psychology) $742,000
  • Exposed: does a leaky blood-brain barrier elevate the risk for obesity in the offspring of obese mothers?
    Associate Professor Christine Jasoni (Anatomy) Standard $740,000
  • Do old males deliver the good epigenes?
    Dr Sheri Johnson (Zoology) $840,000
  • Generating Novel Biosensors to Monitor Oxidative Stress in the Heart
    Dr Peter Jones (Physiology) $805,000
  • Hybrid quantum systems based on rare earth ion dopants
    Dr Jevon Longdell (Physics) $790,000
  • A genomic study of the people of Wairau Bar: health, history and origins of the first New Zealanders
    Professor Lisa Matisoo-Smith (Anatomy) $767,000
  • The ice is melting: how do trace metals in the ocean influence the Antarctic marine ecosystem and global climate?
    Dr Rob Middag (Chemistry) Fast-Start $300,000
  • Small higher-rank graphs, the structure of their operator algebras, and implications for the equilibrium states of the resulting operator-algebraic dynamical systems
    Professor Iain Raeburn (Mathematics & Statistics) $550,000
    Co-Principal Investigators: Professor Astrid an Huef (Mathematics & Statistics), Dr Lisa Clark (Mathematics & Statistics)
  • A baby’s eye view: theory of mind development through exposure to repeated behaviours
    Professor Ted Ruffman (Psychology) $767,000
  • Managing monks: Buddhism, law and monastic control in Southern Asia
    Dr Ben Schonthal (Theology & Religion) Fast-Start $300,000
  • Restriction of gene transfer in pathogenic bacteria by a novel CRISPR-Cas system
    Dr Raymond Staals (Microbiology & Immunology) Fast-Start $300,000
  • Game of clones: unravelling biocide resistance mechanisms in Staphylococcus aureus
    Dr Deborah Williamson (Pathology & Molecular Medicine,University of Otago, Wellington) $490,000

Project summaries:

The ethics of research on clinical data and tissue without explicit patient consent

Dr Angela Ballantyne (Primary Health Care & General Practice, University of Otago, Wellington) Fast Start $300,000

Good quality healthcare depends on medical research. One potentially valuable and under-utilised source of research data is patients' clinical information and tissue samples. Access to this clinical information could support research on which treatments work in real clinical settings with real patients, rather than the controlled and artificial environments of research trials. Yet clinical data and tissue are not routinely used for research. Why not? First many people assume that patients own, and should control access to their clinical information; and second, many assume that research participation must be voluntary. Unfortunately, in many cases, getting consent is too expensive or would undermine the methodology of the research. In this project, I contest both these common assumptions. In their place, I develop a new framework of ethical research using clinical data without patient consent and determine how to best implement this model in order to maximise the social utility of research and minimise the potential harms. I investigate whether patients have a general reciprocal obligation to support the research that supports their medical care; and whether clinical information is co-constructed through a collaborative process involving the patient, doctor and health system.

Identifying novel DNA replication components through harnessing the resource of Mendelian disease

Dr Louise Bicknell (Pathology) $840,000

Mutations underlying single gene (Mendelian) disorders provide a powerful resource to harness to understand cellular functioning and development. In Meier-Gorlin syndrome (MGS), characterised by small ears, small kneecaps and short stature, we identified the first five disease genes which cooperate as a complex to establish sites from which DNA replication commences during cellular proliferation. More recently, we have preliminary genetic data implicating an additional downstream member of the replication machinery in causing MGS (cumulative 60% patient diagnosis). These observations suggest a hypothesis whereby MGS is due to dysfunction of both established and unappreciated DNA replication machinery. Determining additional disease genes from a MGS patient cohort will enable the delineation of novel replication components and, for MGS families, will be clinically valuable. To discover these novel genes, the exomes and genomes of MGS patients will be sequenced using next-generation sequencing technology, and candidate genes will be characterised at both a genetic and cellular level. Given the mesenchymal origins for many specific features in MGS, a mesenchymal stem cell resource will also be established, with a long-term potential to investigate the intriguing link between essential components of cellular replication machinery and MGS developmental anomalies.

A dilute supersolid of polar molecules

Professor Blair Blakie (Physics) $790,000

A supersolid is an almost mythical phase of matter, existing in a confused state that combines the ubiquitous properties of a solid, with the surreal features of a superfluid. In this project we leverage a recent development in the field of polar molecules to propose a pathway to producing a novel dilute supersolid -- almost a billion times more dilute than an ordinary solid. Our work will provide a comprehensive theory for this exotic system, elucidating its fundamental properties, structure and phase diagram, paving the way for its production in the next generation of experiments.

The origins of social inequality in Southeast Asia: an exploration of health and wealth disparity at the emergence of state level society

Associate Professor Hallie Buckley (Anatomy) $767,000
Co-Principal Investigator: Professor Charles Higham (Anthropology & Archaeology)

Social inequality is the common factor in all early state societies, and understanding how it arises is as pressing today as in the past. We seek to trace and explain how this was generated among the ancestors of the civilization of Angkor by integrating archaeology with human biology at the late Iron Age site of Non Ban Jak in Northeast Thailand. This town was occupied during a period of rapid social change and superbly preserved human remains interred within houses present a unique opportunity to test a new model to understand how a social elite arose. Non Ban Jak is a large Iron Age town that rises within encircling moats and banks into two distinct mounds. On the western mound the dead were interred with the implements of manual labour within modest dwellings while the eastern houses became increasingly substantial over time with wealthy burials. It seems likely, therefore, that two classes emerged there, signifying the beginning of social disparity in the community. Identifying the relative wealth and health of the community over time, using new and established archaeology and bioarchaeology methods, is the key to testing a new model of biosocial change for understanding how state formation developed.

Smoothing and inference for point process data with applications to epidemiology

Dr Tilman Davies (Mathematics & Statistics) Fast-Start $300,000

Point process models are used in a wide variety of applications to statistically analyse the patterns formed by spatial data. Critical in these models is specification of functions defining large scale trends in spatial patterns, as well as the dependence structure determining a point's tendency to attract or repel other points. Current methods for estimating these functions can perform poorly, particularly for highly heterogeneous patterns of the type that are observed in many applications. As a result, the significant potential this type of modelling has to improve our understanding of spatial and spatio-temporal phenomena has not yet been fully realised.

In response, our overall aim is to develop statistical theory to improve methods for inference and implementation of flexible point process models in practice. Robust tools will be provided to ensure that model fitting and assessment is reliable. Motivated by examples in epidemiology, the work will extend to developing new approaches to estimating disease risk over geographical regions and thus enhance existing methodology in this and other important and practically relevant areas of application.

Meet the neighbours: evidence for interaction between Lapita colonists and Papuan communities in Papua New Guinea

Dr Anne Ford (Anthropology & Archaeology) Fast-Start $300,000

The Lapita colonisation was the greatest seafaring migration in human history, occupying all of the major island groups in their eastward migration across the Pacific, where they became the ancestors of the Polynesians. The orthodox model for their origin is as an Austronesian movement out of Taiwan, from where they moved into Island South East Asia, and then into the islands of the Bismarck Archipelago of Papua New Guinea, where the culture that we recognise as Lapita was born. Yet major questions still remain as to the nature and origins of Lapita, particularly how much of their culture was a Neolithic package brought out of Taiwan, and how much has been influenced by contact with Non-Austronesians. This is an important question as it cuts to the core of identifying the creation of Pacific cultures. The Triple-I model proposes that the Lapita Cultural Complex evolved from intrusion into new territories, innovation of new technologies, and integration with established communities. Yet most Lapita sites are found on previously uninhabited Pacific islands, therefore what actual evidence is there for interaction with other communities? This project will challenge this fundamental assumption by investigating potential links between Lapita and non-Lapita communities in Papua New Guinea.

Shear force dependent regulation of epithelial Na+ channel (ENaC) and its relevance for blood pressure regulation

Dr Martin Fronius (Physiology) $755,000

The ability to detect mechanical forces and to translate them into biochemical signals is a ubiquitous feature of cells. Epithelial Na+ channels (ENaCs) are regulated by shear force and their localisation in blood vessels implies a function in blood pressure regulation. We will explore the unknown mechanism of how ENaC senses shear force, and discover its role in blood pressure regulation. ENaC activity in response to shear force will be measured in cells (electrophysiology) and isolated blood vessels (pressure myography). These results will reveal a new mechanism that explains how mechanical shear force is converted into the cellular signals that underpin blood pressure regulation.

Targeted, triggered and zero waste prodrug activation

Dr Allan Gamble (Pharmacy) Fast-Start $300,000

Most promising drugs fail to progress to the clinic due to off-target toxicity; thus, the best drug to treat a disorder may not become available to patients. Additionally, costs to the pharmaceutical industry of drug failure are huge, discouraging future investment. As medicinal chemists, we need to find innovative ways to improve drug selectivity and efficacy while reducing toxicity. We propose that toxicity could be reduced through delivering drugs in a more disease-targeted fashion. A prodrug, a drug that has been chemically modified to be invisible to normal, healthy tissue, can be designed to reveal the active drug only at the disease site. However, by-products generated during this process can still cause unwanted toxic effects. To overcome this problem, we will investigate a prodrug that is targeted to and activated specifically at the disease site, converting a normally toxic by-product into the actual drug - a targeted, triggered and zero waste prodrug activation strategy. This new knowledge will have implications for many types of disease including cancer, CNS disorders and infectious disease.

Out of the mouths of babes: Interviewing children in forensic contexts

Professor Harlene Hayne (Psychology) $742,000

In a number of high-profile trials involving allegations of child abuse, convictions were overturned because of the way that children were questioned. The empirical legacy of these trials is that we now understand much more about the best way to interview children in legal settings. Despite this increased understanding, untested interview procedures are still commonly used to collect and present children's testimony, here and overseas. In a series of empirical studies, we will test the effect of these procedures on the content and accuracy of children's reports and on jurors' decisions. The findings will maximise the chances that professionals obtain complete and accurate accounts in cases involving children and shed new light on the way in which a child's testimony should be presented in Court. The findings will also make an important contribution to the New Zealand criminal justice system and in other parts of the world in cases involving child witnesses.

Exposed: does a leaky blood-brain barrier elevate the risk for obesity in the offspring of obese mothers?

Associate Professor Christine Jasoni (Anatomy) Standard $740,000

When a mother is obese during pregnancy, her offspring have an increased risk for obesity. Fetuses developing in this environment show elevated inflammatory mediators, called cytokines, and a leaky blood-brain barrier (BBB). The ability of the BBB to regulate which compounds enter the brain is essential for normal brain function, including control of body weight. This project will use multiple powerful techniques to test the hypothesis that exposure of the fetal brain to cytokines alters BBB formation, which leads to abnormal exposure of the brain to leptin, an essential modulator of body weight, and thus increases risk for obesity.

Do old males deliver the good epigenes?

Dr Sheri Johnson (Zoology) $840,000

Parents influence their offspring in multiple ways, but recent studies have highlighted the role of non-genetic (epigenetic) pathways. Revolutionary new work suggests that life-history challenges experienced by parents, particularly fathers, may be transmitted epigenetically to increase offspring fitness. Collectively, these findings raise the tantalising prospect that older males may pass on more information about their environment through their epigenes, than younger males, thereby providing a fitness advantage to their offspring. Using zebrafish, we will investigate whether environmental challenges (e.g., hypoxia, toxins, alarm cues) experienced as males age affect the fitness of multiple generations, and we will identify key candidate genes for transgenerational effects, by identifying genes that are differentially expressed, as well as differentially methylated. We anticipate that by manipulating environmental experiences acquired within one generation and measuring fitness-related factors over subsequent generations, including genetic and epigenetic profiling, we will determine whether old males do indeed deliver the "good epigenes". Our findings will have significant ramifications on the ongoing nature vs. nurture debate, with broad implications for humans and other systems.

Generating Novel Biosensors to Monitor Oxidative Stress in the Heart

Dr Peter Jones (Physiology) $805,000

Protein oxidation, a consequence of reactive oxygen species (ROS), is a fundamental form of intracellular signalling. ROS production is differentially regulated in discrete regions of the cell, but despite the importance of these 'ROS microdomains' there are currently no tools with the necessary spatial resolution to examine them. In the heart, oxidation is a key regulator of contraction and excess ROS leads to disease, particularly following ischemia-reperfusion injury. ROS augments contraction by increasing calcium release. The calcium release unit in cells of the heart is located within a unique structure, the cardiac dyad, with highly restricted diffusion and localised ROS production. This creates a discrete ROS microdomain. In this project we propose to create mice expressing genetically encoded ROS sensors targeted to the calcium release unit to pioneer the study of the dyad ROS microdomain. We will use these mice to determine when and how ROS within this microdomain is altered. This will allow us to unravel the interplay between ROS and calcium signalling. Understanding how and when the ROS microdomain surrounding the calcium release unit is perturbed will offer a new perspective on how calcium homeostasis is maintained physiologically and becomes corrupted during disease.

Hybrid quantum systems based on rare earth ion dopants

Dr Jevon Longdell (Physics) $790,000

This project aims to substantially improve the ability of rare-earth-ion doped systems to manipulate the quantum states microwave frequency excitations. Superconducting qubits, which operate at microwave frequency, have nearly all the capabilities required for large scale quantum computation, and devices based on rare-earth-ion doped systems can potentially complete the set. We will look at three areas in particular: we will increase the length of time which rare earth ion dopants can store microwave excitations; we develop new techniques for using rare earth spins as quantum memories; and we will investigate the potential of rare-earth-ion dopants in ferromagnetic crystals.

A genomic study of the people of Wairau Bar: health, history and origins of the first New Zealanders

Professor Lisa Matisoo-Smith (Anatomy) $767,000

Wairau Bar is one of the most culturally and historically significant archaeological sites in New Zealand. Dating to the early 14th century, with artifacts that can be sourced to ancestral East Polynesia, it contains one of the largest and best preserved early burial populations in all of the Pacific. Indeed, the koiwi tangata (human remains) from Wairau Bar provide the best representation we have of the founding population of Aotearoa/New Zealand, and thus of early East Polynesia. An ancient DNA genomic study of the Wairau Bar population would allow us to: 1) Identify the likely origins of the first colonists of Aotearoa; 2) Use demographic modelling to reconstruct the population history of Aotearoa through time; and 3) Identify if the founding population carried known genetic markers associated with gout, diabetes and other diseases that affect Maori and Pacific Islanders disproportionately today.

The ice is melting: how do trace metals in the ocean influence the Antarctic marine ecosystem and global climate?

Dr Rob Middag (Chemistry) Fast-Start $300,000

Though often regarded as toxins, metals are required as nutrients for the growth of all organisms. Metals form the reactive centres of enzymes, enabling these to perform biochemical functions, such as oxygen-transport or photosynthesis. As such, trace metals are central to the health of individual organisms as well as entire ecosystems. In the open ocean, the base of the food web is formed by unicellular algae, known as phytoplankton. For certain ocean regions such as the Southern Ocean, trace metals regularly limit the amount of phytoplankton that can grow, and thus the amount of life that can be sustained. Since phytoplankton take up CO2 from the atmosphere, trace metals influence atmospheric CO2 levels and thus the global climate. However, only limited knowledge exists about these algae-trace metal interactions and their susceptibility to a changing climate. Coastal Antarctica harbours large phytoplankton blooms that sustain Antarctica's key higher organisms and are a crucial sink of anthropogenic CO2. This region experiences dramatic changes as temperatures are rising and glaciers are melting. This project will reveal what role trace metals play in the Antarctic ecosystem and give us the ability to predict how its role in global climate will change under future climate scenarios.

Small higher-rank graphs, the structure of their operator algebras, and implications for the equilibrium states of the resulting operator-algebraic dynamical systems

Professor Iain Raeburn (Mathematics & Statistics) $550,000
Co-Principal Investigators: Professor Astrid an Huef (Mathematics & Statistics), Dr Lisa Clark (Mathematics & Statistics)

In mathematical models of physical systems, the time evolution is given by an action of the real numbers on an operator algebra. The equilibrium states of a system are characterised by a relation called the Kubo-Martin-Schwinger condition. This KMS condition has proved important also for systems of purely mathematical origin, where the behaviour of the KMS states often reflects important structural properties of the operator algebra. Our programme seeks the mechanism for this relationship. To find it, we will study two families of systems associated to small graphs. We will introduce a new family of self-similar group actions on the path space of a graph, build operator-algebraic dynamical systems from them, study the KMS states of these systems, and interpret the results in terms of the structure of the underlying algebras. We will study KMS states of operator-algebraic dynamical systems of reducible higher-rank graphs, and expect to find interpretations involving the ideal structure of the underlying operator algebras.

A baby’s eye view: theory of mind development through exposure to repeated behaviours

Professor Ted Ruffman (Psychology) $767,000

Most researchers argue that babies are "mind readers". Mind reading, or theory-of-mind (ToM), entails an understanding of others' desires and beliefs. It is "the most important development in early childhood social cognition", and is reliably linked to children's empathy, popularity and social skills. The idea that babies have a ToM is consistent with the current zeitgeist that infants possess "core innate knowledge". Instead, we argue that infants begin by understanding behaviour, which they learn about by virtue of their exposure to environmental regularities and their innate capacity for statistical learning, enabling learning about patterns. Most regard such ideas as far-fetched. However, we placed a head camera on 39 12- to 24-month-olds to film the world from their perspective, finding that children's ToM was closely related to their exposure to environmental regularities (repeated behaviours such as drinking from a cup over and over), as well as their imitation of such behaviours. Our findings are, however, impotent without a larger longitudinal study. The proposed research will utilize cutting-edge techniques to show that children's rich exposure to environmental information fuels their ToM, findings with profound theoretical implications for children's general development, which will also reveal optimal parenting strategies facilitating their well-being.

Managing monks: Buddhism, law and monastic control in Southern Asia

Dr Ben Schonthal (Theology & Religion) Fast-Start $300,000

Buddhist monks in South and Southeast Asia are widely perceived to embody calmness, compassion and pacifism. Indeed, many of the region's most influential advocates for peace have been Buddhist monks. However, since 2010, Sri Lanka and Myanmar have seen the rise of several new monastic groups that preach messages of hatred and intolerance against religious minorities. This study asks how and why this has occurred. Rather than focusing on the roles played by particular monks, ideologies or politicians, as others have done, this project asks broader questions about how and why Buddhist monastic law--the ecclesiastical regulatory system through which monastic fraternities supervise the discipline and conduct of monks--failed to stop or constrain these groups. In doing this, the project will not only provide a fuller account of the rise of these aggressive monastic groups, it will produce the first detailed study of monastic legal practice in contemporary Sri Lanka, while also helping to advance understandings of the relationships between religious law and civil law in the contemporary world.

Restriction of gene transfer in pathogenic bacteria by a novel CRISPR-Cas system

Dr Raymond Staals (Microbiology & Immunology) Fast-Start $300,000

CRISPR-Cas is a prokaryotic adaptive immune system that restricts horizontal transfer of foreign genetic elements which carry important genetic traits, such as antibiotic resistance and virulence. The three classical CRISPR-Cas systems have been studied extensively over the last few years, and this has led to a revolution in genome editing. Recently, bioinformatic analyses identified a fourth CRISPR-Cas system (Type IV) in several pathogenic bacteria. No experimental information is available about these systems. I will characterise the structural and enzymatic properties of Type IV CRISPR-Cas to address key fundamental questions about this system and its role in controlling horizontal gene transfer.

Game of clones: unravelling biocide resistance mechanisms in Staphylococcus aureus

Dr Deborah Williamson (Pathology & Molecular Medicine, University of Otago, Wellington) $490,000

Chlorhexidine (CHX) is a topical antiseptic used extensively in the clinical setting. We recently discovered a high prevalence of CHX resistance in New Zealand S. aureus isolates, with high rates of co-resistance to another common antibiotic, fusidic acid. In this project, we will determine: (i) the evolution and transmissibility of CHX resistance in S. aureus; (ii) why some strains of S. aureus take up CHX resistance genes, and (iii) whether the presence of these genes confers any bacterial fitness cost. Such knowledge may identify novel strategies and therapeutic targets that limit the emergence and spread of resistant S. aureus.

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