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Marsden Fund backs Otago’s research in best ever round

Clocktower.

Friday, 3 November 2017 10:04am

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The University of Otago has received around $24m in research funding from the annual Marsden Fund.

University of Otago researchers have gained around $24m for 33 world-class research projects in the latest Marsden Fund annual round – the University’s most successful round ever.

The results of this highly competitive and prestigious funding round were announced today, with researchers from across the University’s Divisions of Commerce, Health Sciences, Humanities and Sciences securing funding, in many cases close to $1million each, to lead new projects.

The funding includes 24 standard projects and nine ‘Fast-Start’ projects designed to support outstanding researchers early in their careers.

Deputy Vice-Chancellor (Research & Enterprise) Professor Richard Blaikie warmly welcomed the outstanding success of so many Otago applicants in the highly competitive round, which saw 12 per cent of the preliminary proposals nationally go ahead to secure funding.

“It is pleasing that increased investments from Government in the Marsden Fund have now flowed through to the research community, with such a high number of awards announced this year,” he says.

“We are delighted that the exceptionally high quality of Otago research ideas has been rewarded with our largest success ever, both in terms of the number of researchers supported and the total amount of funding.

“The Marsden Fund represents the most stringent and prestigious national contest of research ideas in New Zealand and Otago’s success in this latest round helps cement our place as a research-led university with a reputation for excellence.”

The Royal Society Te Apārangi administers the Marsden Fund on behalf of the Government. It is regarded as a hallmark of excellence that allows the country’s best researchers to explore their ideas.

Last year, in 2016, Otago researchers received more than $13.7m in Marsden funding to undertake 23 research projects.

Overall this year, a total of $84.6 million (excl. GST) has been allocated across New Zealand research institutions, in the areas of science, engineering, maths, social sciences and the humanities.

This is an increase on the $65 million (excl. GST) awarded to 117 projects last year, due to the increase of $66 million (excl. GST) over four years foreshadowed in the National Statement of Science Investment and confirmed last year’s Budget.

Otago’s Marsden recipients

(Please note only Otago principal investigators and co-principal investigators are listed)

Dr Rosemary Brown, Anatomy (Fast Start)

The neurobiology of maternal behaviour - dissecting the role of prolactin in the medial preoptic area
$300,000

Parental care is critical for the survival of dependent offspring, with maternal care being the predominant form of care in mammals. The brain’s medial preoptic area (MPOA) is central to coordinating changes in how a mother behaves towards offspring. I recently observed a critical role of the anterior-pituitary hormone, prolactin, in regulating the MPOA during lactation, with mothers lacking prolactin receptors (Prlr) specifically in this region abandoning their pups soon after birth. These data provide the first evidence that prolactin action in the MPOA is essential for normal postpartum behavior. Here, I will use our established genetic techniques to target prolactin-responsive neurons in the MPOA during pregnancy and lactation, and measure their activity with calcium imaging, measure their gene expression in these different conditions, and manipulate their activity using chemogenetics. This will greatly contribute to understanding how hormones act in the brain to regulate behaviour.

Dr Aniruddha Chatterjee, Pathology (Fast Start)

Challenging the gene silencing dogma: DNA methylation as a mechanism for gene activation
$300,000

DNA methylation provides a stable mechanism for modulating the gene expression program of a cell. Promoter methylation is associated with chromatin condensation and suppression of gene expression; thus, methylation is widely regarded as a gene silencing mechanism. Strikingly, contrary to this dogma, we have identified several instances where densely methylated promoters coinside with high gene expression. If found to be causal, this observation could overturn tightly held views about the function of DNA methylation. We will use state-of-the-art epigenomic tools and a well-characterised melanoma model to connect methylation with chromatin biology and 3D genome organisation to establish causation for DNA methylation-mediated gene activation in the mammalian genome.

Dr Amita Deb, Physics (Fast Start)

Single photon control of optical phase using ultracold Rydberg atoms
$300,000

Light beams interact with each other extremely weakly in conventional materials. This makes light a fantastic carrier of information, but severely limits its use in information processors. In this proposal, we will create an artificial medium, consisting of atoms at ultralow temperatures, where the interaction is so strong that a single quantum of light (photon) will control the transmission and the delay of an entire beam of light. A key ingredient for photon-based information processing in such a medium is the ability to catch photons and store them for long enough. This has proved a challenging task due to detrimental collisions between randomly moving atoms. By employing a variant of atoms that has a tendency to anti-bunch for fundamental reasons, we will make atoms stay away from each other. This keeps lossy atomic collisions at bay and achieves long-lived storage and an efficient retrieval of photons on-demand. Enabled by this, we will build - piece by piece - a photonic logic module where two light beams act strongly upon each other in a highly controlled way. Our novel and scalable approach addresses a fundamental, long-standing goal of quantum optics and extends the frontiers of photon-based quantum technologies.

Dr Robert Fagerlund, Microbiology & Immunology (Fast Start)

CRISPR-Cas immunity in cyanobacteria
$300,000

Cyanobacteria represent an ancient and diverse phylum with key roles in fresh and marine water ecosystems and global carbon cycles, and are emerging as a vehicle in solar-powered biotechnology. Cyanobacteria are under constant threat of phage infection and one mechanism used to counter these is the CRISPR-Cas defence system. CRISPR-Cas provide prokaryotes heritable and adaptive immunity by initially capturing a genetic memory of the invading element and then using that memory to produce short RNA molecules to specifically target and eliminate the invader. This ability of CRISPR-Cas systems to seek and destroy invading elements has led to a surge in novel genome editing tools. A poorly understood type of system from cyanobacteria appears to be a chimera of two other distinct systems and it is not clear how it functions, although it is very likely to utilise unique features in viral nucleic acid degradation. I will use a combination of genetic, structural and biochemical approaches to investigate the molecular mechanisms used by this system to orchestrate viral defence. In addition, there is potential for discovery of novel enzymes of biotechnical utility and their application in controlling phage infections during industrial cyanobacterial bioprocessing.

Dr Charlotte King, Anatomy (Fast Start)

Planting the Soil and Panning for Gold: Exploring the dynamics of colonial life in Otago
$300,000

Processes of immigration are central to New Zealand national identity and were as important in the past as they are today. The first European settlers flocked to Otago to begin new lives as farmers, leaders of industry or to strike it rich in the goldfields. These people’s individual stories are largely missing from the historical record, which tends to gloss over them in favour of creating state-sponsored narratives. Following the recent excavation of the historic cemetery site of St John’s Milton, however, it is now possible to reconstruct the lives of these early southern European settlers using bioarchaeological techniques. For the first time in New Zealand, cutting-edge isotopic techniques will be applied to settler remains to track changes in mobility, diet and health through their lives. In doing so this project will evaluate whether these first European New Zealanders achieved the better lives they left their homelands for. It will compare the biological histories of the settlers with the historical record in Europe and New Zealand to build a holistic picture of processes of empire-building, adaptation and what it means to be a Pākehā New Zealander.

Dr Adam Middleton, Biochemistry (Fast Start)

Capturing the growth of a destructive ubiquitin chain
$300,000

The post-translational modification of proteins with ubiquitin has a central role in all eukaryotic cells. Disruptions to ubiquitin transfer are associated with many diseases, including cancer and neurodegenerative disorders. Many functions of ubiquitin, including targeting proteins for degradation, rely on construction of ubiquitin chains. Generation of chains requires highly specific, but weak interactions between ubiquitin and E2 enzymes. The weak interactions hamper investigations into the precise mechanism of assembly of ubiquitin chains.

Our prior studies have allowed us to predict the surface of ubiquitin that interacts with an E2 to build degradative chains; and suggest E2-ubiquitin contacts that allow assembly of ubiquitin chains of only one linkage type. To study these interactions in detail we will use phage display to develop forms of ubiquitin that bind tightly to E2s. The isolated ubiquitin variants will be analysed using biochemical techniques and visualised in complex with E2 enzymes by X-ray crystallography. Our goal is to reveal the molecular details that underpin the selective assembly of ubiquitin chains; and to capture the complex that builds degradative ubiquitin chains. The ubiquitin system regulates many, if not all aspects of cellular function, and a detailed mechanistic understanding is central to the development of improved therapeutics.

Dr Mei Peng, Food Science (Fast Start)

Searching for a human sensory ‘fingerprint’ – a personalised index of hedonic eating
$300,000

Fighting against our human desire to over-eat is challenging in a world where food is becoming increasingly accessible, varied, and palatable. Recent data indicate that some people are particularly susceptible to ‘hedonic’ eating for pleasure. While this behaviour is thought to be related to brain networks responding to reward, it is unclear why food holds greater rewards for some people than for others. Because eating is a multi-sensory experience, we predict that the key to understanding this paradox may rest in looking at data across multiple senses. Indeed, tantalising new findings suggest the possibility that we each have a unique sensory ‘fingerprint’ that controls reward-related brain networks and determines individual susceptibility to over-eating. In this project, we will search for this fingerprint and unravel its relationship to hedonic eating using neuroimaging techniques and sensory analyses. This new interdisciplinary research approach promises to revolutionise our understanding of human eating behaviour.

Dr Jonathan Squire, Physics (Fast Start)

The small scales call the shots: the effect of microinstabilities on collisionless cosmic fluids
$300,000

Virtually all of the ordinary matter in the universe is plasma: a fluid that is so diffuse that its ions and electrons cannot recombine into atoms. Very hot and diffuse plasmas, which have weak magnetic fields and infrequent interparticle collisions, are hypersensitive: with any tiny change in the magnetic field, microinstabilities abruptly grow and violently mix the plasma. Despite being enormously smaller in scale than the motions that caused them in the first place, these microinstabilities strongly influence the plasma's macroscale dynamics. We will quantify these effects by developing a new theory for the fluid dynamics (large-scale behaviour) of plasmas under these conditions. This theory will quantify the evolution of microinstabilities, and how they affect the macroscale plasma motions and magnetic fields. Our work will critically improve our fundamental knowledge of this exotic (but widespread) form of matter, will lay the foundation for understanding its turbulent dynamics, and will yield the first practical techniques for simulating such plasmas. These in turn will be crucial for unravelling key astrophysical processes such as galaxy formation, the interaction of the Earth with the sun, and the magnetisation of the universe itself.

Dr Stefanie Zollmann, Computer Science (Fast Start)

Interactive 3D computational videography
$300,000

An emerging paradigm called 3D computational videography uses recently developed image-processing techniques to extract 3D data from videos. However, existing techniques in this area require multiple cameras, or intensive computer processing, or time-consuming human annotation. The aim of the current project is to construct a 3D scene from a single unconstrained video file, with minimal human annotation, in close to real time. After the 3D scene is reconstructed, a user will be able to explore the scene freely, selecting new viewpoints and perspectives. To illustrate, imagine being able to experience a family gathering, captured on a single video, as a fully explorable 3D scene, so that your choices about how to move and where to look can be different from those of the camera operator.
The goal of this project is to advance 3D computational videography with techniques drawn from two existing areas, that have not so far been combined. We will draw on the one hand on well-known computational photography techniques going beyond the boundaries of traditional photography and allowing to extract 3D structure from a single photography and on the other hand on techniques recently developed in augmented reality, that emphasise real-time computer vision and computer graphics.

Associate Professor Greg Anderson, Anatomy

Deconstructing the neuroendocrine requirements for puberty onset and ovulation
$960,000

The timing of puberty and subsequent ovulatory cycles requires exquisite coordination of genes, hormones and brain circuitry. Several neuronal pathways have been identified as being involved, but exactly how they affect reproductive activity is poorly understood. Firstly, we will first characterise the role of three different populations of neurons located at the base of the brain (termed AgRP, RFRP and GALP neurons) in controlling puberty onset and ovulation. This will be accomplished using newly developed mouse models which enable the activity of individual neuronal circuits to be activated or silenced at will. Second, we will determine how these neurons are regulated by the hormones estradiol and leptin, which provide feedback from the gonads and information about nutrient availability. To do this, we will ‘knock out’ the receptors for these hormones from the selected neuronal populations and comprehensively assess puberty onset and a range of fertility measures. Lastly, we will determine the site of action of RFRP neuropeptides by knocking out their receptor from potential target cells. Understanding how these circuits shape reproductive activity will contribute to the development of new treatments for human infertility and suboptimal breeding in animal production systems.

Dr Ashton Bradley, Physics

Making, Probing, and Understanding Two-Dimensional Quantum Turbulence
$905,000

Fluid turbulence subtly shapes our daily existence — we are living in it. It also plays a dominant role in many applied settings including the design of air and water craft, and the prediction of extreme weather events. Yet fluid turbulence remains poorly understood, even though many of its features are universal, appearing in similar forms for a wide range of fluids, and on very different length scales.

In a flattened quantum fluid made of atomic Bose-Einstein condensate, turbulence is stripped down to its bare essentials: the chaotic interaction of tiny quantum whirlpools moving in only two dimensions. Bose-Einstein condensates also offer a promising pathways for studying turbulence due to their precise experimental control and clear theoretical description. While recent advances in manipulation and imaging enable new routes to creating and understanding turbulence in quantum fluids, fully-developed planar quantum turbulence has yet to be observed in nature. We will develop theoretical tools for making, probing, and understanding fully developed two-dimensional quantum turbulence, with close ties to experiments designed to realise these chaotic quantum states. The outcomes of this work will reveal generic features of fluid turbulence, and exotic behaviour unique to fluids obeying the principles of quantum mechanics.

Dr Rebecca Campbell, Physiology

Androgen excess and the female brain
$960,000

Female androgen excess is a distressing issue for a large number of women suffering from polycystic ovary syndrome (PCOS). Our current knowledge of androgen signalling in females is sorely lacking and very little is understood about the potentially critical role that androgen actions have in the female brain. This study will employ new transgenic model approaches and the latest generation of clinically relevant drug therapies to dissect out specific androgen actions in the brain and body throughout female development. We are proposing here to silence androgen signalling in specific developmental windows and in specific tissues and cell types to assess the role of androgen actions in both normal fertility and in states of female androgen excess such as PCOS. The outcomes of this proposed series of experiments will ultimately provide valuable new knowledge on the forefront of basic research aimed at understanding PCOS and steroid hormone signalling in the female brain.

Professor Stephen Cranefield, Information Science

A computational theory of collective action
$460,000

This project will apply computational modelling and simulation to investigate the problem of collective action: explaining how self-interested parties can be motivated to coordinate their action to achieve a common benefit. Problems of this sort include management of a common resource pool (such as a river or a fishery) and collectively reducing carbon emissions. Mathematical models from game theory predict that free-riding behaviour will dominate and cause the collective action to fail. However, a range of social factors, such as the existence of norms, a desire to earn "social capital", and leadership mechanisms have been proposed to explain why collective action will often succeed in practice.

This project uses a computational approach to gain new understanding of the social reasoning underlying collective action problems. We will develop a computational model describing how individuals decide how to act based on personal and social goals and rewards, in combination with social incentives and group coordination mechanisms. Through simulations of various scenarios we will investigate which social factors have the most impact on achieving collective action.

The techniques developed will have the potential for use in building software to advise and assist people to coordinate their actions and achieve collective goals.

Dr Jeffrey Erickson, Physiology

NO Heart: A novel mechanism for modulating cardiac calcium by nitric oxide
$937,000

Nitric oxide (NO) is a key mediator of Ca2+ handling and cellular signaling in the heart, but the targets of NO that coordinate its cardiac effects are largely unknown. Our group recently identified a new target for NO regulation of cardiac physiology, Ca2+/calmodulin-dependent kinase II (CaMKII). CaMKII activation has broad impact on cardiac physiology, including increasing Ca2+ flux, lowering the threshold for Ca2+ entry, and increasing developed pressure. Our work demonstrated that CaMKII can be both activated and inhibited by NO via a pair of parallel mechanisms that result in nitrosylation of two residues (C273 and C290). Moreover, regulation of CaMKII activity by NO directly impacted Ca2+ handling in myocytes by altering the amount of Ca2+ release from internal stores. In this project, we will determine three critical functional consequences of NO-dependent CaMKII activity: 1) the effects on cellular Ca2+ handling and arrhythmogenic Ca2+ leak in myocytes, 2) the effects on Ca2+ entry into myocytes to initiate contraction, and 3) the effects on whole heart function. With this work, we hope to establish a new mechanism by which NO controls cellular and whole heart function, which would provide novel insight into the physiological and pathological processes that underlie cardiac performance.

Associate Professor Peter Fineran, Microbiology & Immunology

Uncovering regulatory networks controlling CRISPR-Cas adaptive immunity
$945,000

Bacteria are constantly exposed to invasive elements, such as viruses and plasmids, and these interactions are key factors in global nutrient cycles, the emergence of pathogens and spread of antibiotic resistance. To protect themselves from these invaders, bacteria have CRISPR-Cas adaptive immune systems, which provide sequence-specific heritable memory of past infections. Immunity relies on the acquisition of ‘memory’ sequences from the invader, which produce short guide RNAs that assist Cas proteins in recognition and destruction of complementary invader genomes. Despite the obvious immune benefits, carriage of these systems can be costly for bacteria. For example, errors in ‘memory’ generation can often result in autoimmunity against the host bacterial chromosome. We propose that extensive regulatory networks exist to maximise CRISPR-Cas immunity when bacteria would be most vulnerable to infection, while also limiting activity when least required – to mitigate autoimmunity. Regulation of CRISPR-Cas activity is poorly understood, and in general there is a paucity of high-throughput approaches to comprehensively identify mutations influencing bacterial gene expression. We will develop and utilise a state-of-the-art single-cell method of broad applicability that combines fluorescent reporters, transposon mutagenesis, fluorescence activated cell sorting and high-throughput sequencing to uncover the pathways involved in the regulation of CRISPR-Cas activity.

Professor Mark Hampton, Pathology, Christchurch

Investigating the role of peroxiredoxin redox relays in cell signalling
$959,000

Hydrogen peroxide acts as a signalling molecule in cells by oxidizing cysteine residues in important regulatory proteins such as phosphatases, kinases and transcription factors. It is currently unclear how these proteins are specifically targeted by hydrogen peroxide. One proposal is that sensor proteins called peroxiredoxins react with hydrogen peroxide, and then relay this oxidation to closely bound target proteins. We are investigating whether these relays operate in human lymphocytes that either generate or are exposed to hydrogen peroxide as part of their normal function. The peroxiredoxins will be removed from the lymphocytes, or mutated in such a way as to disrupt their structure, and we will search for target proteins that are no longer susceptible to oxidation. We will also investigate a putative redox relay between peroxiredoxins and a cytoskeletal protein that regulates the movement of cells, and test the ability of a peptide to disrupt the interaction between peroxiredoxins and the cytoskeletal protein inside cells. The ability to uncouple redox relays would provide a novel antioxidant strategy for protecting cells from pathological levels of hydrogen peroxide.

Professor Janet Hoek, Marketing

Betwixt two worlds? Disruptive technology and negotiating identity change
$845,000

Are electronic nicotine delivery systems (ENDS) a disruptive technology that could dramatically reduce smoking or could vaping instead undermine cessation? Despite agreement that ENDS pose fewer health risks than smoked tobacco, many people do not fully replace smoking with vaping. We will explore this apparent paradox by probing how smokers negotiate new identity positions and which practices they retain, create or relinquish as they begin vaping. We will also examine whether and how vapers transition to become vape-free, thus offering new insights into a previously unexplored question.

Our novel mixed-methods approach will elicit data using longitudinal qualitative interviews, videographic analyses, and ecological momentary assessments, and develop contrasting perspectives on why and when transition from smoking to vaping, and beyond, occurs. We will use emerging social practice concepts to propose an over-arching explanation of how smoking and vaping practices intersect and evolve in relation to other practices. The Government’s plans to liberalise ENDS regulation make New Zealand a unique setting in which to analyse perplexing and unresolved questions about ENDS uptake. The new perspective we propose developing will complement dominant biomedical addiction discourse and provide a richer understanding of how ENDs, a disputed and ambiguous innovation, could improve health and well-being.

Professor Philippa Howden-Chapman, Public Health, Wellington

Eviction and its consequences: representation, discourse and reality, $845,000

Being evicted is a feared experience for tenants. This study is a wide-ranging inquiry into evictions in Aotearoa New Zealand. It first examines eviction of Māori, Pākehā and other ethnic groups historically, including the way their experiences are represented in literature, painting and music. We will compare historical and current law governing evictions in New Zealand with that of other jurisdictions. We will observe the proceedings of the Tenancy Tribunal, which has the power to order the eviction of tenants for non-payment of rent, and interview the Tribunal Adjudicators. Using administrative data and the Tribunal’s records we will analyse who experiences eviction and under what circumstances. In-depth interviews will allow us to investigate the effect of eviction on tenants’ lives, while analysis of open-access landlord online forums will enable us to understand why and how tenants are evicted. Our rounded examination of the fairness and quality of the processes and consequences of eviction in the past and the present will make a unique contribution to social science, socio-legal theory, and understanding the sharp end of housing problems.

Professor Brian Hyland, Physiology

Defining the brain circuits that interface hunger state with reward signalling to guide food consumption
$959,000

Food intake is driven by both by metabolic state, and by the rewarding nature of food and food-associated stimuli. Signals about metabolic state are carried to the brain from the stomach and fat stores by hormones including ghrelin and leptin. Reward signals are processed in the brain by specific circuits. The exact linkages in the brain that enable these processes to be integrated are not fully understood. We will investigate a pathway involving the paraventricular nucleus of the hypothalamus (PVT) that may be key. We will determine if PVT receives information from the brain region where these hormones initially act. Second, we will establish if PVT is positioned to integrate this with information about signals associated with food. Third, we will determine if PVT is appropriately connected to pass this information to structures involved in regulating behavior. To achieve these goals we will combine single neuron recording to characterize responses of brain cells to ghrelin and leptin and to food related cues, with optogenetic methods to selectively activate specific pathways and identify inputs and outputs of recorded cells. The results will provide new knowledge about how the pathways processing food-related signals are interconnected to control feeding.

Dr Karl Iremonger, Physiology

The sex of stress: Understanding sex differences in neural circuits controlling stress
$958,000

Men and women respond differently to acute stress, and this underpins sex differences in stress adaptation, stress resilience and risk for developing stress-related mental health conditions. Corticotropin-releasing hormone (CRH) neurons control the secretion of stress hormones in the body. We propose that differing stress responses between the sexes is determined in part by differences in CRH neuron activity patterns and excitability. We will use real-time recording of CRH neuron activity to determine how stress responses differ in male and female mice and identify the cellular mechanisms that cause these differences. The new information generated will provide a basic science platform for differential evidence-based treatment of stress-related disorders in men and women.

Dr Michael Knapp, Anatomy

TB or not TB - examining the origin and evolution of tuberculosis in the pre-European Pacific
$920,000

The origin and antiquity of tuberculosis (TB) in the Pacific is controversial. TB-causing Mycobacterium tuberculosis complex (MTBC) bacteria are thought to have arrived with European sailors or settlers but TB-like lesions in pre-European skeletal remains from across the Pacific contradict this popular view. We will combine palaeogenetic and macroscopic analyses of pre-European human and animal remains to determine how TB arrived and evolved in the Pacific. This study has the potential to fundamentally alter our understanding of how TB spread around the world and to provide new insights into how MTBC bacteria adapt to human hosts and alter their potential for causing epidemics.

Professor David Larsen, Chemistry

Co-PI – A/Prof Ivan Sammut, Pharmacology & Toxicology
Polymer-Immobilized Carbon Monoxide Donors: Agents for Tissue Protection
$910,000

Once viewed as a “silent killer” through its binding to haemoglobin, carbon monoxide (CO) is now accepted as a cyto-protective molecule with multiple important physiological signalling roles. However, the complexity of controlling low dose CO gas delivery in a clinical setting, combined with the hazardous consequences of any gas leak, have been acknowledged as significant impediments for its use in gaseous form. CO-releasing molecules (CORMs) provide a much safer alternative as administration of the therapeutic dose can be closely controlled. Most CORMs are small molecule transition-metal carbonyl complexes that have shown beneficial effects but have inherent toxicities prohibiting human applications. We have recently developed a novel small molecule, metal-free, organic class of CORMs that shows valuable promise as an additive in organ/tissue transplant solutions, and as a prophylactic in heart bypass surgical applications. Using our technology we will develop these compounds further for human applications by immobilising them onto polymer supports to overcome problems with cellular toxicity and aqueous solubility. Our polymers are designed for ease of use by improving solubility in biological media, and by delivering clinically relevant CO-release profiles. Additionally, synthesising polymers with trackable markers will help answer fundamental controversies surrounding the mechanism of action of CORMs.

Associate Professor Richard Macknight, Biochemistry

Lost in translation: Discovering how plant genes are regulated
$895,000

The precise control of gene expression is vital for an organism’s growth and survival. While transcriptional regulation (DNA to mRNA) has been extensively studied, translational regulation (mRNA to protein) has largely been ignored. The conventional view is that eukaryotic mRNAs encode just one protein. However, it has recently been discovered that large numbers of plant and animal mRNAs have short protein coding sequences (called upstream Open Reading Frames or uORFs) before their main protein-coding region. These uORFs regulate translation.

We recently identified a uORF that controls translation of the rate-limiting enzyme for the biosynthesis of ascorbate (vitamin C), the main antioxidant that protects plant cells from environmental stress damage. The uORF within the ascorbate biosynthetic gene enables it to be translated during stress conditions, when other genes are prevented from being translated to conserve metabolic energy. The uORF also functions to precisely and rapidly regulate ascorbate levels.

Here, we will dissect the mechanisms by which uORFs in the ascorbate biosynthesis gene, and in two other important plant stress response genes, regulate translation in response to drought stress. To improve plant tolerance to stress, uORF sequences will be altered by gene editing to enhance the expression of key stress response genes.

Professor Sally McCormick, Biochemistry

New players in protein recycling
$957,000

Twenty percent of people have high levels of a form of blood cholesterol called "Lp(a)" which predisposes them to heart attacks. Lp(a) consists of a low density lipoprotein (LDL), otherwise known as the "bad cholesterol" particle, with an additional protein called "apo(a)" attached to it. Much is known about how Lp(a) causes heart attacks but less is known about how it is cleared from the blood. Even less is known about what its function is.
We recently discovered a new clearance pathway for Lp(a) that operates via a plasminogen receptor called "PlgRKT". This pathway leads to Lp(a) uptake by liver cells and subsequent recycling of the apo(a) component. Our research aims to characterise the newly identified Lp(a) uptake pathway and establish the function of apo(a) recycling. Since apo(a) is known to bind oxidised lipids, released from stressed or dying cells, and fibrin from the breakdown of blood clots, we hypothesise that the function of apo(a) recycling is to clear these toxic waste products from circulation. Our research will generate new knowledge about Lp(a), plasminogen receptors and protein recycling biology. The project will also lay the foundations for developing novel Lp(a)-lowering therapies.

Associate Professor Karen Nairn, College of Education

Putting Hope into Action: What inspires and sustains young people’s engagement in social movements?
$840,000

Hope for social change is a powerful catalyst for taking political action. Our aim is to understand the role of hope in the politicisation of young people (aged 18-29) in New Zealand. How might hope for social change inspire, and sustain, young people’s political action? Brexit, Trump, and recent UK elections have generated considerable debate about the role of the ‘youth vote’, challenging assumptions of young people as apolitical. Working with six collectives of young people, which are addressing social and environmental injustices, we will explore how they put their hopes for social change into action. Deploying activist history interviews and ethnographic methods, such as participant observation and social media, we will investigate what sustains young people’s collective engagement. Each collective will be invited to present their vision for the future as a ‘living manifesto’. The project will fill a significant research gap in New Zealand while making an important contribution to international research on politics, new social movements, and the role of hope. As a society, it is imperative we understand what kinds of futures young people are working towards because their hopes and actions could transform the lives of future generations.

Professor Robert Poulin, Zoology

Microbes at the helm: are microbiomes shaping parasite phenotypes?
$890,000

The microbiome revolution is rapidly changing how we study ecology and evolution, as researchers increasingly realise that much of an organism’s phenotype can be attributed to its metagenome (combined DNA of its resident microorganisms). Parasitic organisms also have their own microbiomes. Can these shape parasite biology and host-parasite interactions? This could have far-reaching implications for our understanding of parasitism and the development of new anti-parasite therapies. Using two flatworms which parasitise native aquatic animals, we will address this question, testing for ontogenetic, inter-individual and geographic variation in parasite microbiomes and experimentally quantifying their impact on parasite development and, ultimately, their phenotype. Our research will use a set of powerful tools ranging from metagenomic sequencing to experimental manipulation of microbiomes, to explore how bacteria shape what parasitic worms actually do.

Professor David Prior, Geology

Stretching ice to the limit: New flow laws for ice sheets
$960,000

Ice deformation and ice-sheet flow control future sea level. Although strain in glacial ice is high, laboratory studies of ice deformation that yield mechanical data have only been conducted to low strains (<30%). Rock deformation experiments suggest that microstructural change and mechanical weakening in ice should continue to strains of >500%. Therefore, it is very likely that existing models underestimate the contribution of deformation to ice-sheet flow. We propose new torsion experiments (twisting a cylindrical sample) to quantify microstructural and mechanical evolution of ice to high strain (>500%). We will derive a new high strain ice flow law, from experiments at temperatures between -5°C and -30°C and across two orders of magnitude in strain-rate. We plan to test the extrapolation of the new flow law to natural (slow) strain rates in two ways; firstly by measuring the stresses needed to deform glacial samples at natural strain-rates and temperatures and secondly through a field experiment to constrain the deformation conditions in the shear margin of an Antarctic glacier. Micromechanical models will be used to explore how rates of different grain-scale processes contribute to microstructural and mechanical evolution and to provide simple strain-dependent parameters to use in large-scale ice sheet models.

Dr Bruce Russell, Microbiology & Immunology

Unraveling the molecular basis for vivax malaria's unhealthy attraction to human reticulocytes
$960,000

Plasmodium vivax (Pv) is the most widely distributed and difficult to cure form of human malaria. Pv is certainly the most important cause of malaria in the Asia Pacific region. Difficulties in diagnosis, treating the dormant liver stage and the recent spread of drug resistant Pv have provided impetus for vaccine development against vivax malaria. The ability of Pv to cause disease is dependent on invasion of immature red blood cells (reticulocytes). How Pv identifies and invades reticulocytes remains unknown. We aim to identify the specific blood cell receptors and corresponding parasite proteins used to invade human reticulocytes. To do this, a proteomic shortlist of reticulocyte receptors will be targeted by neutralizing antibodies/knockdowns in Pv invasion assays. The identification of the reticulocyte specific receptors and corresponding ligands will aid in the development of vaccines against vivax malaria.

Dr Harald Schwefel, Physics

Microresonator frequency combs through second-order nonlinearities
$910,000

Frequency combs are light sources whose spectrum consists of numerous equally-spaced lines. They were first invented in 2000, triggering a string of breakthroughs; the Nobel Prize followed in 2005. In 2007, a revolutionary new way of frequency comb generation emerged: a laser beam launched into a microscopic resonator spontaneously transformed into a comb! Unfortunately, the third-order nonlinear light-matter interactions that underpin the transformation gives rise to complex instabilities, and do not permit straightforward access to the visible and mid-infrared spectral regions.

In this project, we will experimentally demonstrate an entirely new paradigm of microresonator frequency combs based on second-order light-matter interactions, whose unique and unexplored advantages have full potential to enable stable frequency combs and access to new spectral regions. Through synergetic combination of theory and experiment, we will leverage distinct second-order processes to demonstrate novel microresonator comb sources satisfying critical needs at three distinct spectral regions: (i) the near-infrared, (ii) the visible, and (iii) the mid-infrared. The developed second-order microresonator frequency comb sources will represent an entirely new technology that has full potential to offer unprecedented performance for a myriad of applications, including multi-wavelength telecommunications (near-infrared), imaging (visible), and molecular spectroscopy (mid-infrared).

Dr Catherine Smith, Centre for Materials Science and Technology

Whakaarahia anō te rā kaihau! Raise up again the billowing sail! Revitalising cultural knowledge through analysis of Te Rā
$845,000

Despite the centrality of sailing in New Zealand history, only one customary Māori sail survives. The sail (Te Rā), probably collected by Cook (c.1768-79), is in closed storage at the British Museum, London. Te Rā has been exhibited once, but has not been experienced in New Zealand since collection. Little information exists about customary Māori sails, despite revitalisation of ocean-voyaging waka and related knowledge systems which have had demonstrated benefits for Māori cultural health. This collaborative and interdisciplinary project, connecting Mātauranga Māori and science, brings experienced weavers and scientists together to unlock the cultural knowledge only available through study of Te Rā. Enquiry into Te Rā provides a vehicle for all New Zealanders to engage with the story of an unparalleled journey that brought people to the last unexplored landmass, and the birth of Aotearoa. As the physical embodiment of cultural knowledge of voyaging, Te Rā also shows evidence of the emergence of a distinctively Māori response to new plants, animals and sailing. This project is at the nexus of Mātauranga Māori and Western science, providing a model for robust knowledge development beneficial to iwi, practitioners and academics through comprehensive research on the sole remaining Māori sail, Te Rā.

Associate Professor Claudine Stirling, Chemistry

How does the Earth stop global warming? Testing climate stabilisation during ‘hyperthermal’ events
$960,000

The Earth is in the midst of a climate crisis, with a carbon cycle disturbance comparable to those that drove biological turnover and even mass-extinction events in geological history. The side-effects of warmer global temperatures are already occurring, including ocean acidification, toxic phytoplankton blooms, and expansions of oxygen deprived conditions in the oceans. It is less well known that these threats are also negative feedback mechanisms that remove carbon from the atmosphere, and eventually re-stabilise the climate on geological timescales. The climate recovery process, however, is poorly constrained, and it is not known exactly when or how the natural climate system will return to ‘normal’. Anthropogenic activity might have even delayed the next natural glaciation cycle. We will use novel geochemical proxies and biogeochemical modelling to trace the action of negative feedback mechanisms during past global warming events. These will be applied to a series of events that represent a range of CO2 emission scenarios, analogous to those we face in the future. We will constrain the feedback mechanisms of the climate system to better understand the lifespan of human-induced climate change, providing crucial boundary conditions for modelling future climate scenarios.

Dr Megan Wilson, Anatomy

Understanding the cellular and molecular drivers governing a unique whole body regeneration phenomenon in a chordate model
$820,000

Regeneration is a basic biological phenomenon that involves a complex temporal and spatial
interplay of molecular signalling cascades, cell divisions, chemical and mechanical stimuli.
However, the nature of signals that instigate the process of regeneration and the biology of effector cells remain elusive. A striking example of regeneration is the process of whole body regeneration phenomenon in Botrylloides, where a fully functional adult regenerates in under two weeks from isolated minute fragments of blood vessels. Our research programme will combine cell-tracing, gene editing and genomics methods to determine the molecular and cellular basis of regeneration in this amazing animal.

Associate Professor Rachel Zajac, Psychology

The Secret Life of Traumatic Memories
$695,000

Traumatic memories seem to have a secret life. Influential, but pseudoscientific, clinical theories would have us believe that memories for traumatic experiences are jumbled, and recalled in bits and pieces with parts missing. That is, the memories are said to be fragmented, lacking coherence. In this pseudoscientific view, fragmentation is harmful—caused by the allegedly special mechanism by which the brain encodes only "shallow" aspects of trauma, forgoing deeper conceptual processing. The idea is that with the right therapy, what's called "traumatic amnesia" fades; the fragmented memories fill out, and coherence increases. This view rests entirely on the 40-year-old presupposition that traumatic memories behave differently from non-traumatic memories. But there is no scientific evidence that the harm of fragmentation, the special encoding mechanism, or the "traumatic amnesia" actually exist. More likely, we propose, is that fragmentation is not unique to trauma; instead, people appraise fragmented traumatic memories in unique ways. In doing so, they set in motion a chain of behaviours that shape their memories, their psychological wellbeing, and sometimes their very willingness to question what they remember. We will connect the links in this chain.

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