University of Otago researchers have won $13 million of grants from the Marsden Fund.
A total of 22 research projects at Otago received funding in this year's round, between them accounting for about a quarter of the money the Marsden Fund provided to the university sector this year.
The fund, administered by the Royal Society, supports research in science, technology, social sciences and the humanities.
Deputy Vice-Chancellor (Research and Enterprise) Professor Richard Blaikie yesterday congratulated the successful researchers.
"They are outstanding in their fields, continuing the proud tradition at Otago for excellence in research that contributes to both national and world knowledge across a wide spectrum of disciplines," he said.
"They have done extremely well to successfully attract the funding in a round that is so highly competitive."
Otago's Marsden recipients
Professor Greg Cook - $847,826
Pumping lysine to achieve metabolic homeostasis during infection
Mycobacterium tuberculosis is a highly effective pathogen that has evolved numerous mechanisms to successfully invade, replicate, and persist in humans. We have identified an unprecedented role for a lysine transporter (exporter) during M. tuberculosis infection and mycobacterial growth on lipids. We hypothesize that lysine export is crucial for achieving metabolic homeostasis by acting as a "relief valve" or novel energy spilling mechanism. We will employ molecular biology and genetics, and appropriate in vivo models to address this hypothesis. The elucidation of molecular mechanisms governing metabolic homeostasis could identify critical pathways for targets in drug discovery or vaccine design in the fight against tuberculosis.
Professor Andrew Mercer - $800,000
BAFfled: how does orf virus defeat the BAF cellular defence mechanism?
It was shown recently that a eukaryotic protein, BAF, is part of the cell's innate defences against viral infection. Most poxviruses defeat this defence by using a viral kinase to phosphorylate BAF. However, we have identified some poxviruses that lack this kinase. How then do these viruses counteract BAF? We will identify the factor these viruses use to defeat BAF and characterise its mechanism of action. This project will define a new mechanism by which viruses evade cellular defences and shine new light on the activities of BAF, an essential cellular factor.
Dr Claudine Stirling - $739,130
Global ocean anoxia during ancient 'greenhouse' climates: Prospects for a warming world
Today, the world's oceans are generally oxygenated, but there have been times in the past when warm, 'super-greenhouse' climates prevailed and vast expanses of the oceans were devoid of oxygen. These so-called 'ocean anoxic events' caused immense chemical change in the oceans and devastated Earth's ecosystems for up to half a million years at a time. We will use variations in the isotope composition of uranium, a trace element affected by anoxia that is emerging as a powerful new palaeo-redox tracer, in conjunction with other trace element isotope systems, to reconstruct the timing, duration and extent of anoxia across known anoxic events of the Mesozoic Ocean. Importantly, we will quantify the degree to which oxygen depletion extended from the deep ocean into the shallow photic zone, which currently remains uncertain. These high-resolution records will constrain the mechanisms leading to extreme oxygen deprivation in the oceans, and in turn, will have a direct bearing on predicting future climate-change impacts over the coming decades, given the rapid expansion of anoxic waters that has occurred in recent years due to global warming.
Dr Keith Ireton - $760,870
Role of host cell polarized exocytosis in spread of bacterial pathogens
Many bacterial pathogens actively promote their spreading between human cells. One of the key events in spreading these pathogens is the formation of ‘protrusions'- bacteria enclosed in extensions of the host plasma membrane. Overall, mechanisms of protrusion formation are not well understood. Listeria monocytogenes is an important bacterial cause of food-borne illnesses. Protrusion formation and spread of Listeria in the intestinal epithelium is likely critical for disease. Our preliminary data indicate that Listeria protrusion formation requires several host proteins that promote polarized exocytosis in the human cell. Polarized exocytosis is the fusion of cytoplasmic vesicles with select regions of the plasma membrane. Our findings have led to the novel hypothesis that formation of Listeria protrusions may involve the localised insertion of host membrane, thereby providing membrane and/or human proteins needed for protrusion production. We will use genetic and microscopy-based approaches to test this hypothesis. Specifically, we will determine if the human exocyst, a protein complex involved in polarized exocytosis, is required for Listeria spreading. In addition, we will examine if Listeria protrusions are active sites of exocytosis.
Associate Professor Alistair Knott - $652,174
Does language syntax mirror the structure of sensorimotor cognition?
We can use language to talk about the world we live in. This involves converting rich sensory/motor representations of the world into high-level symbolic representations. How this happens is largely an open question in cognitive science, because language and sensorimotor processing are currently studied in separate disciplines: linguistics and sensorimotor neuroscience. Our novel claim is that these disciplines are deeply connected. We propose a linking hypothesis, positing detailed connections between influential theories of language syntax (Chomsky, 1995) and sensorimotor cognition (Ballard et al., 1997). In our hypothesis, the syntax of a sentence reporting a concrete episode in the world directly describes the sensorimotor routine through which the episode was perceived. Our hypothesis makes detailed predictions about the episode-perception routine associated with any concrete sentence. The project will test these predictions, for four selected sentence types. In each case, we will build a computational model of the actual sensorimotor routine through which the episode type in question is perceived, motivated directly from experimental evidence. We will then compare this routine to that predicted from syntax. If the predicted routines match those motivated experimentally, this will furnish evidence that syntactic analyses directly deliver information about neural processing; an exciting finding for neuroscience.
Professor David Craw - $630,435
Gold growth in situ: nanoparticles to nuggets
This project will quantify, for the first time, the biogeochemical controls on gold mobility in groundwater systems. Most extant models for gold nugget growth have been developed in ancient geological terranes without quantitative constraints on nugget-forming environments. Our previous work has shown that New Zealand river gravels host excellent examples, some unique, of gold precipitates at the nanoparticle and small nugget scales. This gold mobility has occurred in groundwater under near-surface conditions in a range of geological and geochemical environments, including some in very young (late Quaternary) deposits. Our study will take advantage of the current New Zealand gold mining boom to gain access to new alluvial gold mines that are exposing unoxidised waters, mineral precipitates, and gold samples below the water table where gold mobility has occurred, and possibly is still occurring. Our results will lead to the development of the first field-based, fully quantified, model for low-temperature gold nugget growth. This model will have two strands: a biogeochemical pathway to be developed using our results as constraints, via existing collaborations with experimental and field microbiologists; and an inorganic geochemical pathway which will integrate New Zealand geological, climatic, and groundwater data on sites in which gold has been mobilised and precipitated.
Professor Sally Brooker - $739,130
Designer spin crossover: towards nanoswitches, sensors and displays
Spin crossover complexes can act as nano-switches because they can switch between two states, low spin and high spin (which have distinctly different colour, size and magnetism). Switching between these states occurs on perturbation, for example by a change of temperature or pressure, or by irradiation, and in special cases exhibits a memory effect. Such complexes are attractive for the development of functional nano-components, and represent a ‘bottom up' approach to ‘molecular' computers, rather than the current ‘top down' approach of etching smaller and smaller circuits onto silicon chips. Hence considerable international attention is being directed at developing such nano-components and the associated fundamental science that underpins this research. This programme targets the preparation, characterisation and tuning of designer spin crossover molecules that might act as nano-switches, and the incorporation of additional functionality to fine-tune them and to facilitate assembly of new switchable materials in solution and/or on solid supports, challenging goals. Applications of these novel spin crossover materials may ultimately include use as nano-memory components, sensors, displays or biomarkers. The knowledge and skills of a PDF, PhDs and MSc students will be greatly enhanced by the wide range of experiences inherent in this cutting-edge and highly collaborative research.
Professor Richard Cannon - $773,913
Fungal drug resistance - not as simple as A-B-C
Multi-drug-resistant fungal infections of humans have high mortality rates. This resistance is usually caused by the overexpression of pleiotropic drug resistance (PDR) ATP-binding cassette (ABC) membrane protein transporters that have a distinct topology compared to other well-studied classes of ABC protein. PDR pumps are predicted to contain large extracellular loops (ELs) that are not present in other ABC proteins. We have extensive preliminary evidence from the analysis of both site-directed and resistance-conferring mutations that existing models of PDR transporters are inaccurate. We propose that the unique ELs form ‘lids', and transmembrane segments form ‘gates', essential for substrate selection/transport and inhibitor binding. We will use our powerful set of tools that include an efficient heterologous expression system and over 300 site-directed mutants of PDR efflux pump Cdr1p, including a functional cysteine-less pump, to test this hypothesis. We will employ molecular genetic, biochemical, and biophysical techniques in three complementary
approaches to show that the lid and gate structures contribute to a novel ABC protein transport mechanism and represent unique, specific, targets for clinically important PDR proteins.
Professor Sylvie Chetty - $773,913
Entrepreneurial Networking and Foreign Market Entry Decision Making
The purpose of this project is to adopt recent advancements in entrepreneurship theory to better understand the decision paths of small and medium sized enterprises (SMEs) in their efforts to penetrate global markets. While entrepreneurship is considered in many countries to be an important way to create employment and socio-economic and technological progress, we have little theoretical understanding of how entrepreneurs make decisions about which foreign markets to enter. We use an emerging theory from entrepreneurship- effectuation- as well as theories about the internationalisation process and social and business networks from the international business literature. These theories form the foundation of our qualitative research aimed at developing new conceptual insights and hypotheses about SME pre-internationalisation. We then conduct quantitative research to test our hypotheses using a large cross-country sample of SMEs in New Zealand and Australia. This study advances theory development in both entrepreneurship and international business. It provides managers and policy makers with new paradigms for boosting exports by encouraging non-exporters to enter international markets and inexperienced exporters to improve their internationalisation capabilities. As entrepreneurs gain more knowledge about foreign markets they increase their international sales and subsequently foster opportunities for employment growth.
Professor Richard Walter - $773,913
Maximising success in a new land: the role of Wairau Bar in the systematic colonisation of New Zealand by Polynesians
The colonisation of Aotearoa by East Polynesians was the final step in the prehistoric human diaspora that began in Africa 60,000 years ago. It was also the most remarkable, involving the movement of at least 400 people across 3000 km of open ocean, from a tropical to a cool-temperate environment. Apart from the technological achievement of getting here, this required radical reorganisation of cultural behaviours. This project investigates a new theory for the Polynesian colonisation of Aotearoa that fits recent discoveries in archaeology and biomolecular sciences. Current models emphasise a lengthy adaptation phase followed by expansion from a founder population. They assume the process was slow and gradual and was based on demographic pressures. We argue that colonisation was a deliberate, planned migration from an interaction sphere in Hawaiki that involved specific social and behavioural strategies for exploring the country and establishing viable populations. We believe that the process began with the establishment of a base settlement and that the best candidate for such a place is the extraordinary Wairau Bar site, where the richest, most diverse assemblage of early East Polynesian artefacts was discovered. This model more closely reflects oral tradition and is compatible with contemporary migration theory.
Dr Mikkel Anderson - $717,391
Controlling the microscopic world: Few-atom quantum dynamics
Can we prepare one, two, three neutral atoms in a specific quantum state and measure the outcome of the ensuing dynamics? Can we use this strategy to watch the emergence of macroscopic behaviour like Josephson tunnelling or the laws of thermodynamics, on an individual event level? We will attempt to do this after first establishing ultimate control over the quantum state of individual atoms by laser-cooling them into the ground state of optical microtraps. Deforming the optical potentials will initiate quantum dynamics, which we will observe through our single-atom sensitive optical microscope. In this way we can watch the strange quantum phenomena unfold, whose existence is often confirmed only indirectly. We will see individual atoms penetrate barriers too high to surmount and identical atoms interfere to produce unexpected outcomes, and how these processes are suppressed by controllable decoherence. Combining the supreme control and flexibility of our experimental platform with state-of-the-art numerical and theoretical modelling provides us with unprecedented tools to observe and understand the emergence of macroscopic behaviour in few body systems of increasing complexity. Our work will provide detailed fundamental insight into the microscopic world and enable fascinating applications in quantum computing, quantum simulations, and in precision metrology.
Professor Anthony Kettle - $847, 826
Tying Knots in Proteins with Chlorine Bleach: Novel post-translational modifications catalyzed by mammalian peroxidases
Haem peroxidases are ubiquitous in biology and use hydrogen peroxide to promote a vast array of essential oxidative reactions. Myeloperoxidase is the most characterised mammalian peroxidase. It is a major protein in white blood cells and converts hydrogen peroxide and chloride to chlorine bleach or hypochlorous acid. White blood cells use chlorine bleach to kill bacteria but it also promotes tissue damage during inflammation. It is toxic because it oxidizes myriad biological molecules; particularly methionine and cysteine residues in proteins. Recently, we found that it couples methionine or cysteine residues to juxtaposed amine groups, forming irreversible cross links. We will assess whether these cross links are formed by white blood cells and exacerbate inflammatory pathologies. Another human peroxidase, peroxidasin, has just been discovered to catalyse similar indispensable structural cross links between methionine and lysine residues in adjacent strands of collagen. However, there are uncertainties about how peroxidasin promotes these cross links. The major conundrums concerning peroxidasin that we will address are what hypohalous acid does it generate to tie the cross links, where is it active, and does it promote post-translational cross links in other proteins. We predict that mammalian peroxidases use hypohalous acids to tie knots in many proteins.
Professor Neil Gemmell- $826,087
Ladies before gentlemen - investigating the molecular basis of female to male sex change in sequentially hermaphroditic fish
Most plants and animals irreversibly differentiate becoming either males or females. However, in some groups, notably fishes, individuals begin life as one sex and reverse sex sometime later in response to social cues (sequential hermaphroditism). Sex reversal in sequential hermaphrodites is complete, entailing radical restructuring of the gonad, alterations in morphology, and modifications to behaviour. The molecular basis of this stunning transformation is unknown, but is of intense interest, not only as a means to enhance our understanding of sex determination and differentiation, cellular commitment and tissue re-engineering, but also as a spectacular example of phenotypicplasticity in response to environment. Using the ubiquitous NZ spottie, together with two distant tropical relatives, the bluehead and three-spot wrasse, both leading models for sex reversal, we will undertake a series of experiments to determine the genetic pathway underlying this stunning transformation. We will use in the field ecological manipulations to produce a time series of
samples taken during the process of sex reversal, and couple these with state-of-the-art gene expression analyses and comparative genomic approaches, to identify both the primary trigger and subsequent genetic cascade that results in female-male sex reversal in these fishes.
Professor Jamin Halberstadt - $652, 174
The causal role of religious belief in managing death anxiety and intergroup discrimination.
Although religious belief is a universal feature of human societies, cognitive scientists have only recently attempted to explain why. We propose a series of rigorous experiments to test the effects, and potential functions, of religious belief. First, we will study the emotional consequences of belief: Perhaps the most influential, but untested account of why we believe is that we fear our own death, and are therefore drawn to entities that exhibit, and sometimes have the power to grant, immortality. Our research will develop a means of temporarily shifting religious belief to observe its causal effects on attitudinal, behavioural, psychophysiological, and hormonal responses to death. Second, and relatedly, we will study the effects of religious belief on national, ethnic and religious intergroup discrimination, which many researchers believe represent strategies for achieving "symbolic immortality" to ward off fear of death. Understanding the dynamics of belief, emotion, and behaviour is urgent. Equipped with expertise, theory, and methodological innovations for manipulating and measuring belief, we expect to make significant advances in understanding just how belief helps - or hurts - individuals and societies.
Dr Thomas McLean- $391,304
Global Romantics: How the Porter Family Changed Nineteenth-Century Art and Literature
Recent research in the British Romantic era has called attention to the importance of families, religious communities, and social networks in the creation of cultural works. However, few scholars have examined the lives and works of nineteenth-century British novelists Jane and Anna Maria Porter and their brother, the artist and traveller Robert Ker Porter. Yet their works influenced and altered some of the major literary and artistic movements of their era, and their lives offer fascinating, new perspectives on a remarkable range of fields. The Porters' story explores the challenges faced by women in the literary marketplace, and the global network of friends and family women writers utilised to further their careers. But it also extends our knowledge of Romantic-era archaeology, museum development, and the links between art, literature, and politics. Thousands of unpublished Porter family letters survive in US and UK collections, and these provide a unique opportunity to study both the public and private expressions of a British family with connections to five continents. A critical study of the Porter family will offer new information on the historical novel, women authors, cosmopolitanism, and the nineteenth-century family as a global, creative network.
Dr Lucy Jack - Fast Start - $300,000
You can't go home again: forensic evidence for changes in ecosystem function following mainland extinction of pinnipeds.
Loss of Earth's biodiversity caused by humans disrupts ecological processes and destabilises ecosystems. Human impacts on ecosystems can result in food webs becoming shorter, less complex and less stable. To restore the health of New Zealand's marine ecosystem we need to know what it was like before human contact and how it has changed. For example, fur seals and sea lions were once common around our coasts but were hunted down to remnant populations at the very margins of their range. Now their populations are returning, but can they fit back in? Apex predators such as seals and sea lions are food web integrators. Discovering changes in their trophic position can reveal changes in the structure of the whole food web on which they rely. As the last major land mass settled by humans, New Zealand harbours a uniquely well-preserved record of human exploitation, readily discernible from archaeological records. We will use forensic analysis of a time-series of fur seal and sea lion bones from archaeological deposits to describe the structure of prehistoric marine food webs and to track changes in ecosystem structure, from the advent of human exploitation in New Zealand to the modern day.
Dr Harold Bernhardt - Fast Start - $300,000
In the cradle of the double helix: a novel proposal for the origin of life
The 'RNA world hypothesis' proposes that RNA once functioned as the exclusive genetic material and biological catalyst. However, RNA is a complex molecule made up of phosphate, ribose and nucleotide bases, and its evolution is unclear. Yakhnin has recently proposed a scenario in which RNA precursors underwent selection for stability prior to the advent of replication and Darwinian evolution; however, his model does not consider the ultimate source of the nucleotides. We propose that the nucleotide bases arose from simpler precursors that formed stabilizing interactions between the twin strands of a ribose phosphate double helix. Further, in line with Granick's hypothesis of biosynthetic pathways recapitulating evolution, we propose that these simpler precursors were intermediates of the modern de novo purine biosynthetic pathway. Notably, nearly half of the reactions in this pathway have been shown to or are proposed to occur spontaneously, suggesting they could have occurred prebiotically. Proposed RNA precursors will be computer-modelled, synthesized, and their structure and stability determined. This proposal promises not only to expand our understanding of early RNA evolution - according to the ‘RNA world hypothesis', possibly the origin of life itself - but also provide novel insights into the structure of modern RNA.
Dr Miriam Sharpe - Fast Start - $300,000
Bioluminescent Microcrystals from the Firefly Squid
The firefly squid from the Western shores of Japan glows with an intense blue light from light organs on their arm tips when they are disturbed. The light is emitted by microscopic protein crystals contained within the light organs. Proteins that crystallise inside living creatures are rare, and no other bioluminescent organism is known to glow in this way. We plan to find out how these fascinating glowing crystals produce light by revealing their atomic architecture. We will isolate the microcrystals from the squid and determine their structure using X-rays at a specialist micro-focused beam line at the Diamond Light Source Synchrotron. We also plan to generate the crystals artificially, which will enable us to characterise them further. This is a crucial step towards using the intense light from this bioluminescence system as a new tool in biotechnical research.
Dr Michael Stevens - Fast Start- $300,000
Between Local and Global: A World History of Bluff
This project is a historical case study of Bluff between the years 1800 and 2000 that will re-shape thinking about New Zealand's economic development and race relations. As Southland's sole deep-water port, Bluff was a key entry point for goods, people, livestock and ideas central to the lower South Island's colonial development. In return it dispatched primary products to points throughout the British Empire. Even though it became an important cog in an imperial system, the port attracted and retained a relatively large number of Kai Tahu people. This project examines whether this constituted a Maori attempt to avoid or find a place within the economy, if this Maori presence shaped the port's evolution, and whether or not the port underwrote or rewrote Maori lifeways. In exploring these questions, this study responds to calls for regional histories of Maori economies and their transnational linkages, and focuses very strongly on the interplay between economics, place, and community formation. In examining these factors and uncovering the way they sustained a robust Maori community, this project speaks to large historiographical questions in New Zealand. It also challenges the insular approach that tends to shape thinking and writing about the Maori past.
Dr Priscilla Wehi - Fast Start -$300,000
Colonisation impacts and the decoupling of human cultural and ecological systems
In the face of rapid environmental change, what determines whether species go extinct? Domesticated and commensal species have travelled with humans throughout the world and are integrally woven into the development of culture. Research on biodiversity losses has focused on ‘wild' species, yet human-associated species are not exempt from decline. Using New Zealand as an exemplar, we examine the decoupling of human-ecological linkages in Maori and Moriori society during the pre-European and colonial period. With an innovative interdisciplinary approach we explore the role of societal and ecological transformations in the losses of domesticated and commensal populations. Initially, we focus on kuri and kiore, two introduced mammals valued in traditional society. We interrogate oral and written archives and consult with elders in a kaupapa Maori approach to identify cultural attitudes and feedback loops, particularly after European colonisation. Using stable isotope analysis and Bayesian modelling, we construct isotopic niches for kuri and kiore, and model human-ecological coupling and decoupling under resource stress. Results from the research will reveal relationships between cultural worldviews, changing bio-economics and extinction vulnerability. We compare these findings with other indigenous perspectives on human-associated species, and answer fundamental questions about feedback loops leading to
decoupling in human-ecological systems.
Dr Jeffrey Erickson - Fast Start - $300,000
Identifying the mechanisms by which CaMKII regulates cellular signaling in the diabetic heart
The incidence of diabetes mellitus is rising in New Zealand and worldwide. Diabetic patients are more than twice as likely to develop cardiomyopathy compared to nondiabetics, while sudden heart failure remains the most common cause of mortality amongst those with diabetes. However, the signalling pathways that connect diabetes to cardiac pathology have not been determined. Recent work from my former lab group focused on identifying novel mechanisms by which elevated glucose availability during hyperglycemia activates Ca2+/calmodulin dependent kinase II (CaMKII). Activation of CaMKII plays a nodal role in cardiac cell death and arrhythmia, suggesting that hyperglycemia-induced CaMKII activity may connect diabetes to heart failure. Here we propose to examine the role of CaMKII activation in apoptotic signalling and the genesis of arrhythmic events during hyperglycemia and diabetes. Moreover, we will test the hypothesis that inhibition of CaMKII activity protects against pathological signalling in the diabetic heart. From these studies, we hope to gain new insight into the signalling pathways that mediate cardiac pathophysiology in the context of diabetes.
Dr Christina Riesselman - Fast Start - $300,000
Windows onto warmer worlds: sea ice, nutrient utilization, and primary production on the Wilkes Land margin, Antarctica
The East Antarctic Ice Sheet (EAIS) is generally accepted to act as a stable, permanent feature of the Antarctic cryosphere, however diverse lines of evidence suggest that its marine margin is prone to retreat during episodes of global warmth. The ice sheet is grounded below sea level on the Wilkes Land margin, making this a promising location from which to develop records of maximum EAIS sensitivity to past warm climates. Earth has not experienced the level of warmth predicted for the coming century since the late Pliocene, ~3 million years ago. We will assess Pliocene East Antarctic sea ice and primary productivity, which respond directly to changes in climate and ice sheet proximity, from two marine sediment cores recovered from the Wilkes Land margin. We will apply a paired proxy approach, using (1) the established environmental affinities of diatom assemblages to reconstruct sea ice, open water, and stratification, and (2) the stable isotopic composition of diatom-bearing sediments to reconstruct biogeochemical cycling. This reconstruction will address key uncertainties in the potential for a sensitive portion of the East Antarctic Ice Sheet to be destabilized by the level of warming anticipated to result from anthropogenic CO2 release.