Friday 4 November 2022 4:09pm
Grant recipients are, top row from left, Dr Amandine Sabadel, Professor Blair Blakie and Dr Charlotte King, then bottom row from left, Professor Claudine Stirling, Dr Daniel Pletzer and Professor Gregory Cook.
Has deforestation in Aotearoa forced native insects to change colour to ensure their survival? Can metals help solve a growing global antimicrobial resistance? How did the first Māori communities really engage with moa and what can we learn from that today?
All of these questions, and more, will be answered by University of Otago researchers who have been granted prestigious Royal Society of New Zealand Marsden grants.
Twenty-four Otago academics were today announced as successful in their bid for a 2022 Marsden grant, worth a total of almost $19 million.
Twenty-one researchers and their teams were awarded standard grants, and four fast start grants which recognise emerging researchers.
Deputy Vice-Chancellor Research and Enterprise Professor Richard Blaikie offered his congratulations to the recipients of the highly competitive grants.
“This latest impressive performance continues the University’s strong record in gaining external research funding and reflects the ongoing strength of the University’s research culture,” he says.
Professor Jon Waters, of the Department of Zoology, has been granted $960,000 for his project to test for evolutionary changes in New Zealand’s animals linked to loss of forest - using native insects as a model system.
“By comparing the same species inhabiting both forested and cleared habitats - using a combination of genetic and ecological approaches - we hope to see if, and how, they have evolved in response to recent deforestation.”
A key question in biology concerns the ability of species to adapt to environmental change, he says.
“As the world changes fast, we need to understand the extent to which our wildlife can evolve in response to these new challenges.
“Internationally, perhaps the most famous example of rapid evolution is the case of the peppered moth in the United Kingdom, a species which quickly changed colour in response to pollution.
“In New Zealand, loss of forest is perhaps the most obvious and widespread human-driven environmental change. We suspect that deforestation has fundamentally shifted the evolutionary trajectories of many of our native species,” Professor Waters says.
Professor Richard Walter, of the Archaeology Programme, has been granted $870,000 to investigate how Māori communities interacted with moa.
“Aotearoa is possibly the only place in the world where it is possible to observe - archaeologically -the demise of a megafauna following interaction with humans. Despite the common cry that moa were hunted to extinction, we really have few clear ideas about what avian and human behaviours actually led to the demise of moa.
“Understanding this question will shine light on extinction problems worldwide,” Professor Walter says.
His team, who includes Dr Chanel Phillips (Ngati Hine, Ngapuhi), Co-director of Te Koronga Indigenous Science Research Theme, will drawing on new data from archaeology and molecular zooarchaeology, and adopt the Māori principle of mahinga kai as the central framework of analysis.
“Our underlying principle is that moa hunting cannot be seen as an isolated practice but would have been a component of complex mahinga kai systems.”
Professor Gregory Cook, of the Department of Microbiology and Immunology, has been granted $934,000 to research a world-wide health problem.
“Antimicrobial resistance (AMR) is a rapidly evolving global emergency that threatens many of the achievements of modern medicine. In 2019, the deaths of nearly five million people were associated with AMR bacterial infections and 1.27 million deaths were directly attributed to AMR,” Professor Cook says.
In the face of rising AMR and a dwindling supply of effective antibiotics, there has been a resurgence of interest in exploiting metals such as zinc for novel metal-based antimicrobials or as chemical adjuvants, which increase the efficacy of antibiotics, he says.
Professor Cook and his team has previously demonstrated that the zinc ionophore PBT2 can resensitise high-priority drug-resistant bacterial pathogens to multiple antimicrobial.
“This study will provide essential insight into driving the development of unique antibiotic adjuvants for breaking AMR and breathing life into antimicrobials that have become discarded due to widespread resistance. It will also provide a molecular framework for understanding AMR reversal more broadly in other bacterial pathogens.”
Nationally, 113 research projects were allocated almost $78 million in this round of Marsden grants.
Dr Charlotte King, Anatomy - $870,000, Connecting to the Colonial: Exploring the power of archaeological science to humanise the past
We aim to reconstruct the lives of some of the first Pākehā settlers in New Zealand. Until now, colonial bioarchaeology has focused on understanding broad-scale details of individuals’ lives. However, the preservation of hair, nails and teeth in colonial cemetery contexts gives us the opportunity to apply time-resolved biochemical techniques to reconstruct life experiences on a week-to-week, month-to-month and year-to-year basis. We will use advanced archaeological science techniques such as cortisol, compound-specific amino acid, and elemental analysis to characterise the psychosocial, nutritional, and environmental stresses experienced in nineteenth century New Zealand. By reconstructing these everyday hardships, we will breathe new life into colonial stories. We will then collaborate with descendant groups to communicate these life histories to the public. We will take a trans-media approach, using a variety of communication strategies to appeal to groups of different generations. These approaches will then be examined using a historical consciousness framework to assess which approach provides the best connection between the people of the present and those of the past.
Professor Stephen Robertson, Women's & Children's Health (DSM) - $960,000, A regulatory role for the septin cytoskeleton in brain development
As neurons differentiate they develop specialised subcellular regions while still preserving intracellular communication between these compartments. We have identified a neurodevelopmental disorder caused by mutations in SEPT2, encoding a protein that forms macromolecular cytoskeletal scaffolds in cells. We hypothesise that these mutations impair the formation of the Axonal Initial Segment, a structure that separates the cell body from the axon, by a dominant negative mechanism. How Septin2 influences protein-protein interactions, microtubular networks and murine cortical development will be addressed. These studies will reveal how a poorly understood cytoskeletal component regulates the function of brain neurons during neurodevelopment in humans.
Associate Professor Yiwen Zheng, Pharmacology & Toxicology - $870,000, Counting on your Ears
Numerical cognition is a fundamental ability for everyday life, but its underlying neurobiology is largely unexplored. A 3-way interaction, however, has been suggested between space, time and number. The vestibular system, which detects head movement in 3D, is important for both spatial and temporal information processing. Up until now, however, the vestibular system has never been directly demonstrated to be involved in numerical processing. We propose that the vestibular system may also play an important role in numerical cognition. We will test our hypothesis by activating or inactivating the vestibular system in rats, then testing the effects on a numerical discrimination task and on the activity of neurons in brain areas processing numbers and vestibular information. This study will thus elucidate a novel mechanism by which animals process numbers, which may dramatically change the way that scientists understand numerical cognition and our understanding of the interaction between space, time and numbers. Our study of the vestibular system may also provide a common mechanism for spatial navigation, temporal orienting and elementary numerical computations.
Grant recipients are, top row from left, Jess Pasisi, Professor Jon Waters and Dr Jonathan Squire, then bottom row from left, Associate Professor Keith Ireton, Dr Laura Gumy and Dr Marco Brenna.
Dr Laura Gumy, Anatomy - $960,000, Molecular and cellular organisation underlies the asymmetric regeneration of sensory axons
Mammalian sensory neurons are nerve cells that transmit sensory signals from the environment (e.g. heat, touch, pain) to the brain via cell extensions called axons. To do so, sensory neurons have a unique morphology where a single axon emanates from the neuronal cell body and splits into two axonal branches. The “peripheral” axon innervates peripheral tissues, whereas the “central” axon innervates the spinal cord. Despite being two parts of the same neuron, the two branches respond differently to injury. The peripheral axon can regenerate towards its target tissues, whereas the central axon cannot regrow. At the molecular level, the cause of this regenerative asymmetry remains unknown. We recently discovered key molecular differences between the two axons that might account for their different regenerative abilities. We will take advantage of cutting-edge genetic, microscopy and in vitro and in vivo axon injury/regeneration assays to uncover the fundamental cell biology of sensory neurons and identify the mechanism(s) responsible for regulating axon regeneration.
Professor Richard Cannon, Oral Sciences - $934,000, Membranes matter: how membrane lipids control Candida albicans Cdr1 structure and function
Membrane proteins (MPs) are responsible for vital cell functions and many are important drug targets. Dysfunctional MPs cause several human diseases and their overexpression frequently causes drug resistance in microbial pathogens and in human cancer cells. The drug resistance of the major human fungal pathogen Candida albicans is caused by the overexpression of MP Cdr1. Structure-directed drug design can overcome MP-mediated resistance, but this relies on correct MP structures. It is evident that MP structure and function depend on the complex composition and architecture of biological membranes. Unfortunately, many MP structures to date are unnatural because they were generated with detergent-solubilized MP preparations stripped of their structure- and function-defining lipid components. We will use styrene maleic acid polymers to extract and purify homogenous, functional, C. albicans Cdr1 nanoparticles together with their essential native plasma membrane lipid constituents. Cryo-electron microscopy and 3D-reconstruction of these particles will generate the first structure for the native Cdr1 MP-lipid complex. We will compare this structure with the structure of detergent-purified Cdr1 MP preparations, and we will investigate how membrane composition affects Cdr1 structure and function. Understanding how membrane-lipids interact with Cdr1 will have fundamental implications for future MP research and for structure-directed drug design.
Professor Michelle Glass, Pharmacology & Toxicology - $960,000, Unlocking the therapeutic potential of the human cannabinoid CB1 receptor: Rational design of novel allosteric modulators
Cannabinoid CB1 receptors in the brain and periphery are important in a broad range of physiological processes. As such they have been proposed as useful targets to treat diseases including pain, psychosis, appetite stimulation and glaucoma. Direct activation of the receptor is however linked with adverse effects, such as psychoactivity. Allosteric modulation provides a more nuanced approach to targeting receptors by enhancing the activity of the natural ligands. This is hoped to lead to improved therapy through a more natural pattern of activation, with less adverse effects. This project will apply computer modelling, chemistry and pharmacology to understand the ways in which modulators interact with CB1 to enhance receptor activity. This will enable us to design novel compounds that modulate CB1 receptors that could become lead molecules for drug discovery.
Dr Amandine Sabadel, Zoology - $960,000, Can isotope maps and environmental DNA reveal the mysterious marine life of New Zealand eels?
The spawning sites and larval dispersal routes of Aotearoa New Zealand’s taonga longfin (Anguilla dieffenbachii) and shortfin (A. australis schmidtii) eels remain unclear, making the life cycles of these eels one of the great unsolved mysteries among migratory species. While satellite tracking is usually the approach employed to follow an animal’s movement, it has proven difficult with eels. As such, we propose to use a combination of cutting-edge techniques based on biochemical and molecular markers. We will generate isotope maps of the western South Pacific Ocean and use them to pinpoint eels to visited locations based on age-specific isotope values stored in their inert tissues. The resulting models will integrate isotopes, environmental DNA and RNA, and hydrographic data to track the migration of eel larvae on their journey to their coastal, estuarine, and freshwater habitats in Aotearoa New Zealand. This unique study will provide critical data that will lead to a better understanding of the spawning area and migration patterns of eels, help fill in critical life-history knowledge gaps that can inform their protection and insure their continual recruitment, shed light on their vulnerability to climate change, and pave the way for studying other migratory marine species
Associate Professor Peter Jones, Physiology - $958,000, Role of CK2 phosphorylation of the ryanodine receptor in seizures+
Ryanodine receptor (RyR2) mediated calcium release is a fundamental step in neuronal and cardiac function. A growing body of evidence suggests that spontaneous calcium release (SCR) through RyR2 leads to neuronal hyperexcitability and seizures. A common way in which RyR2 is regulated is through phosphorylation. Dogma states that, in excess, phosphorylation of RyR2 is pathological, increasing SCR and neuronal hyperexcitability, leading to disease. However, we recently identified that RyR2 is phosphorylated by a new kinase, CK2, and that this reduces SCR and protects against pathology in the heart. Whether CK2 phosphorylation also reduces neuronal SCR, hyperexcitability, and protects against seizures is unknown. We have developed two transgenic mouse models, where RyR2 is either always phosphorylated by, or can never be phosphorylated by, CK2. Using real-time calcium imaging and behavioural measurements in these animals we will determine if CK2 phosphorylation of RyR2 prevents neuronal hyperexcitability and protects against seizures. Phosphorylation by other kinases alters SCR due to changes in single channel function and RyR2 ultrastructural arrangement. Therefore, we will also determine if CK2 phosphorylation alters SCR via these same molecular pathways. Combined, this will confirm the role of CK2 phosphorylation of RyR2 in protecting against SCR, neuronal hyperexcitability, and seizures.
Professor Jon Waters, Zoology - $960,000, Adapting to NZ's deforested ecosystems: testing for human-driven shifts in insect colour
Are human impacts reshaping the evolutionary dynamics of our native species? Many NZ ecosystems have been drastically altered by deforestation over recent centuries, and we predict that these sudden changes have had direct evolutionary consequences. For example, widespread loss of lowland forests has shifted the compositions of our freshwater ecosystems, changing the way in which native species need to interact. Our project will examine how deforestation has driven rapid changes in insect colouration linked to shifts in species interactions. We will use genomic approaches to understand how different insect lineages have rapidly evolved similar adaptations to human-driven environmental change.
Professor Gregory Cook, Microbiology & Immunology - $934,000, Disrupting Bacterial Metal Ion Homeostasis to Break Antimicrobial Resistance
Antimicrobial resistance (AMR) is a rapidly evolving global emergency. We have demonstrated that the zinc ionophore PBT2 can resensitise high-priority drug-resistant bacterial pathogens to multiple antimicrobial classes in vitro and in vivo. The mechanisms underpinning this resensitisation remain unknown but may hold the key to breathing life into antimicrobials that have become discarded due to widespread resistance. We hypothesise that the dysregulation of metal ion homeostasis functionally impairs genetic and metabolic resistance pathways resulting in antimicrobial resensitisation. To address this hypothesis, we will use methicillin-resistant Staphylococcus aureus as a model system to elucidate the molecular determinants of PBT2-Zn mediated β-lactam (e.g., oxacillin) resensitisation. We will achieve this by combining complementary genetic, metabolic, and biochemical approaches to uncover the AMR breaking network triggered by PBT2-Zn. This study will increase our understanding of how changes in bacterial metal ion homeostasis trigger critical physiological and metabolic pathways to sensitise bacterial cells to antibiotics. Understanding this will provide essential insight into driving the development of unique antibiotic adjuvants for breaking AMR and provide a molecular framework for understanding AMR reversal more broadly in other bacterial pathogens.
Associate Professor Keith Ireton, Microbiology & Immunology - $829,000, Exploitation of host mechanotransduction by Listeria monocytogenes
Eukaryotic cells can sense physical forces and convert these stimuli into biochemical signals that control physiological responses. This process of 'mechanotransduction' provides a rapid and effective means of activating signal transduction pathways that regulate a variety of responses, including polymerization of the actin cytoskeleton. Many bacterial pathogens induce remodeling of host actin filaments in order to infect human cells. However, it is currently unknown if any bacterium does so by exploiting host mechanotransduction. In this proposal, we test the hypothesis that the food-borne bacterium Listeria monocytogenes co-opts mechanotransduction mediated by the human receptor E-cadherin to stimulate actin polymerization that promotes infection of host cells. We will test this hypothesis using several cell biological approaches, including confocal microscopy imaging of tension sensors, RNA interference, and proximity-dependent biotin identification (BioID). If successful, this work will be the first demonstration of a bacterial pathogen subverting host mechanotransduction for infection.
Professor Claudine Stirling, Geology - $929,000, Metal micronutrients: Major players in the Southern Ocean's carbon sink
The expansive Southern Ocean controls global climate by drawing-down atmospheric carbon-dioxide into the ocean’s interior via marine primary production within the ‘biological pump’. This process is limited by the supply of trace-metal ‘micronutrients’, such as iron and zinc, but future-climate projections are constrained by traditional ‘macronutrient’-based productivity tracers that are not ideally suited to Southern Ocean climate reconstructions. We will couple the excellent discriminatory power of newly emerging micronutrient tracers of marine productivity based on the stable-isotope systems of iron, zinc and cadmium with state-of-the-art Earth-system climate-modelling to directly quantify the influence of trace-metal micronutrients on marine productivity during the ‘last glacial cycle’. This interval spans the global warming and cooling transitions of the past 140 thousand years and includes similarly abrupt climate reorganisations as those occurring today. We will apply our calibrated micronutrient-isotope tracers to fossil-plankton extracted from a basin-wide, latitudinal-transect of Southern Ocean marine sediments to reconstruct micronutrient uptake by primary producers as a high-resolution time-series across the ‘last glacial cycle’. We will interface our micronutrient-focused records with an Earth-system climate model that uniquely integrates micronutrient-limitation of marine primary production to assess the efficiency of Southern Ocean carbon-dioxide removal during major climate reorganisations and improve future-climate projections.
Grant recipients are, top row from left, Matthias Fellner, Melanie Laird and Professor Michelle Glass, then bottom row from left, Nicholas Green, Associate Professor Peter Jones and Dr Philip Brydon.
Dr Marco Brenna, Geology - $929,000, Pinpointing the volatile driver for sudden large-scale volcanic eruptions
Sudden and violent volcanic eruptions, such as the 15th January 2022 Hunga explosion in Tonga are rare and catastrophic events. This large event was unexpected from a volcano that in the recent past had only produced mild, small-scale eruptions. The 15th January event followed a month-long period of low-magnitude activity with the climactic explosion not conforming to standard models of gas-driven explosive volcanism. We have obtained a unique collection of samples from the 2021/2022 eruption, as well as historic (2009, 2015) and pre-historic eruption deposits at Hunga volcano that are now largely destroyed. This provides a one-off research opportunity to understand one of the most enigmatic eruptions of modern volcanology. We will quantify the role of magmatic gases and the compositional heterogeneities of melt and crystals to reconstruct the pre-eruptive plumbing system geometry. Rates and drivers of natural magmatic processes will be simulated with novel experiments of crystallization, magma rise and melt/gas separation. We will model the timescales of crystal growth in changing magmatic environments and hence reconstruct the sequence of events leading up to the catastrophic 15th January explosion. Our quantification of the spatial dynamics and timescales of magmatic processes will inform new models of sudden large volcanic explosions.
Dr Daniel Pletzer, Microbiology & Immunology -$960,000, Molecular mechanisms underlying pathogen-pathogen interaction during skin infection
The management and treatment of infections caused by multidrug resistant pathogenic bacteria is a difficult endeavour. If not adequately addressed, our society will encounter a situation where physicians will have no viable options to treat bacterial infections. In many chronic infections, pathogenic microorganisms persist despite our immune system. Recent studies indicate that co-infection with multiple bacterial species cause increased morbidity and result in poorer treatment outcomes compared to single-species infection. The molecular mechanisms of how bacteria interact to exacerbate infection remain unclear. We will employ a novel polymicrobial mouse skin infection model to investigate factors underlying polymicrobial infections involving multiple bacteria. Specifically, the interactions between different pathogenic bacteria will be investigated using state-of-the-art high-throughput transposon mutant library sequencing (Tn-Seq), live animal imaging technologies (IVIS), and transcriptome sequencing (RNA-Seq) coupled with flow cytometry and fluorescence-activated cell sorting (FACS) to isolate bacteria from skin abscesses at key time points during infection. This work will lead to a better understanding of how pathogens synergise to cause disease and may provide fundamental mechanistic information useful in developing new therapies. This is especially important since antimicrobial resistance is on the rise in Aotearoa and we urgently need new therapies to address this important health issue.
Professor Blair Blakie, Physics - $937,000, Growth, life and death of a supersolid
About half a century ago theoretical physicists speculated on a weird state of matter – the supersolid – possessing crystalline structure (solidity) and frictionless flow (superfluidity). The long quest to find a supersolid was successful in 2019 using a dilute quantum gas of highly magnetic lanthanide atoms. This project will develop a theory to describe the life cycle of these supersolids – from the dynamics of how they emerge during cooling or a temperature quench, through to their eventual demise due to atomic loss. Our approach involves developing and implementing a novel thermal (finite temperature) theory that describes the partially-coherent and incoherent dynamics of the system. This will enable us to capture the interplay of thermal fluctuations and supersolidity. We will apply this theory to quantify the finite temperature phase diagram of dipolar supersolids and to identify a pathway for labs to produce the next-generation of supersolids that exhibit two-dimensional crystalline structure.
Dr Jonathan Squire, Physics - $937,000, A theory for coronal heating through turbulence mediated by the helicity barrier
Just above its surface, the Sun's atmosphere (corona) suddenly jumps to more than a million degrees, escaping the gravitational pull to become the solar wind. Understanding how this occurs––specifically, how energy is released from tangled magnetic fields into heat––is an 80-year-old conundrum known as the "coronal heating problem." Because the solar wind directly influences Earth, damaging satellites and power networks and causing the beautiful aurora, it impacts both astrophysics and everyday life. Its solution requires understanding the complex interplay between the Sun's magnetic-field structure and local heating, while agreeing with decades of precision observations. We recently discovered an effect, the "helicity barrier," which changes how random, turbulent fluctuations become heat as they propagate outwards from the Sun. The effect has promising traits, unifying two previous theories and matching features of the solar wind observed by spacecraft. But, our results remain idealised so far. Using supercomputer simulations, this proposal will expand them into a theory of helicity-barrier-mediated coronal heating, characterising how global magnetic-field structures regulate local dissipation of fluctuations into heat. The goal is to unify seemingly disparate observational constraints under one framework, making testable predictions for the cutting-edge spacecraft that are currently exploring deeper into the corona than ever before.
Dr Philip Brydon, Physics - $937,000, Superconductors that survive ultra-high magnetic fields: Revealing the role of symmetry
Superconductivity is a quantum state of matter where electricity flows without resistance. It has found widespread application in the electrical generation of magnetic fields, but the strength of such magnets cannot exceed a critical field which destroys the superconductivity. The conventional theory of the superconducting state predicts an upper limit for this critical field, which is satisfied by almost all superconductors. Our 2021 Science paper reported that superconductivity in CeRh2As2 survives fields far larger than this expected limit; furthermore, a distinct new superconducting state appears at high field strengths. We explained this unique behaviour as arising from the symmetries of its crystal lattice, which strongly constrains the motion of the electrons in the material. These symmetries are not uncommon, however, and may explain mysterious high-field behaviour observed in other superconductors. Moreover, we propose that they can enable the observation of long-predicted excitations of the superconducting state, and may be exploited to realize novel microelectronic devices. This motivates our planned research to develop a comprehensive understanding of the role of these symmetries in superconductivity. Our work will both fundamentally extend the microscopic understanding of superconductivity, and also open new frontiers in superconducting technology.
Professor Richard Walter, Archaeology -$870,000, Moa hunting, mahinga kai and Maori economic practices - 1300 to 1450 AD
Moa hunting was essential for the success of the first Māori communities establishing themselves in New Zealand (Aotearoa) around 1300 AD. But moa, the world’s largest bird, were extinct a century later – one of the world’s last, and possibly fastest, megafaunal extinction. A century of moa and moa hunting research has seen progress in understanding the taxonomy, biology, and ecology of moa. Archaeological sites have produced abundant moa bone as food remains and as tools. Yet we still know virtually nothing about how Māori communities actually engaged with these animals. This study focusses on the role of moa and moa hunting in supporting our first communities. Drawing on new data from archaeology and molecular zooarchaeology we adopt the Māori principle of mahinga kai as the central framework of analysis. Mahinga kai is a structured, adaptable set of practices around food procurement, resource management and landscape acculturation. Our aim is to learn how moa were integrated into mahinga kai knowledge and practice in fourteenth century Aotearoa. This will contribute unique understandings of Māori lifeways in the first critical century of our history, and contribute to a new, indigenous science methodology in Aotearoa based on mātauranga Māori (traditional Māori knowledge systems).
Grant recipients are, top row from left, Professor Richard Cannon, Professor Richard Walter and Professor Stephen Robertson, then bottom row from left, Associate Professor Steven Mills, Associate Professor Tim Hore and Associate Professor Yiwen Zheng.
Associate Professor Steven Mills, Computer Science - $723,000, 3D Shape Analysis with Geometric Declarative Networks
We will advance 3D shape analysis, going beyond current coarse classification methods to fine-grained classification on the basis of shape alone. To achieve this we will use recently proposed declarative network architectures to integrate collaborative representations and geometric deep learning. This combination will allow more detailed analysis of 3D objects. In particular we will be able to distinguish broadly similar objects on the basis of local shape features. Our initial application is in archaeology, specifically traditional Māori stone tool manufacture. Subtle variations in the waste flakes from this process make them an ideal target for our proposed methods.
Associate Professor Tim Hore, Anatomy - $934,000, Building and breaking the Androgen Clock
Epigenetic clocks can predict cellular age with surprising accuracy, using only DNA as an input. Recently developed epigenetic clocks can also forecast other important measures such as time to death; however, their utility and functional significance is under-explored. Here we propose to create the first 'Androgen Clock', an epigenetic clock that can predict long-term exposure to androgens, with preliminary data suggesting it will be accurate to within months. While this will be a useful tool in itself, with the potential to improve disease diagnostics and food verification, we believe the Androgen Clock will be most valuable in providing fundamental new understanding about epigenetic clock biology. Because male-typical androgens are entirely dispensable, we will use the Androgen Clock to understand what makes epigenetic clocks ‘tick’. We will also use epigenetic editing to test if Androgen Clock sites (as a model for other epigenetic clocks), have any biological significance beyond predictive potential. In doing so, we will overturn understanding in the currently expanding field of epigenetic clock research.
Fast Start Grants - $360,000
Melanie Laird, Anatomy - Seasonal prostate plasticity – a novel model for the regulation of cell proliferation
Prostates of mammals that breed seasonally undergo dramatic seasonal enlargement and regression. Rapid shifts between proliferation and apoptosis are rare in adult tissues to prevent uncontrolled growth and cancer, yet, remarkably, prostate shifts in seasonal breeders are both controlled and reversible. These species are thus excellent models for understanding the mechanisms of controlled growth, however, how prostates shift between activity and inactivity is largely unknown. Here we propose an ambitious comparative study to identify the specific genetic patterns that switch the mammalian prostate ‘on’ and ‘off’. We will identify candidate genes uniquely expressed in prostates of seasonal breeders (brushtail possum and red deer) relative to ‘control’ species (opossum, black rat) that breed year-round (Q1), then test these for functional roles by manipulating their expression in cultured cells (Q2). As experts in mammalian biology and RNA-seq, with access to all required resources, we are ideally placed for success. This will be the first comparative study of prostate transcription, and the first to identify functional roles of prostate genes involved in seasonality. Our study will shed light on the fundamental processes controlling cell proliferation and apoptosis, as well as on how diverse mammalian species overcome the shared challenges of seasonal reproduction.
Matthias Fellner, Biochemistry - Targeting newly discovered biofilm-associated virulence factors of Staphylococcus aureus to treat chronic bacterial infection
Staphylococcus aureus is a human pathogen that is a major cause of chronic infections in New Zealand and around the globe. Infections like bacteraemia, pneumonia, or endocarditis are difficult to treat due to the presence of its unique biomolecular matrix, a biofilm. S. aureus modifies the lipid component of this matrix to establish colonisation, form the biofilm and adapt to environmental challenges. The underlying enzymatic processes that perform the lipid modulation are unknown. The aim of this proposal is to understand how lipid hydrolysis by lipases (lipid cleaving enzymes) enables S. aureus biofilm lipid modulation to establish infection, grow biofilms and counter the immune system and certain antibiotics. This knowledge will be used to inform the development of candidate drugs to target these enzymes to provide more effective treatment options for S. aureus chronic biofilm-based infections. The long-term prospect is a significant improvement of health and wellbeing of individuals and populations in New Zealand and world-wide.
Nicholas Green, Chemistry - Covalent Biomolecular Conjugates as Potential Progenitors to Primordial Cooperative Biological Systems
The transition from primordial soup to primitive organism is a process which may be understood by characterising the fundamental interactions of (bio)molecules likely present on the primordial earth. Interactions of increasing complexity – yet still based on readily rationalisable and ultimately predictable principles of structure and reactivity – must have eventually given rise to biochemistry. These interactions will be studied by preparing and characterising biomolecular conjugates. Resulting observations of the physical and chemical behaviours of these conjugates will improve our understanding of the role of such molecules in bringing about the cooperative behaviour necessary for life’s emergence, and our knowledge of structure, reactivity and mechanism in chemistry and biology.
Jess Pasisi, Te Tumu: School of Maori, Pacific & Indigenous Studies - Mapping Niue texts in and beyond Aotearoa: Expanding on New Zealand Realm connections to Niue through archival texts
The central aim of this project is to explore the joy and pleasure tau tagata Niue gain from engaging with Niue texts. Specifically, the project aims to identify, catalogue, and critically analyse Niue texts throughout history, examine how tagata Niue engage with Niue texts in contemporary repositories, and expand our shared understanding of Indigenous literary connections between Niue and Māori, Realm nations, and broader global Indigenous communities. Four key clusters of research questions extend from this central aim: 1) What published Niue written texts exist in contemporary repositories? What is the context of how these texts came to be published? And how are Niue people engaging with these archives? 2) How do Niue published written texts fit within a wider corpus of Niue cultural production and self-expression? How can Niue texts in contemporary archives be engaged in ways that extend beyond the archives themselves and into the broader community? 3) How can we engage with the layered complexity of Niue texts in multi-lingual forms? How are Niue texts being engaged in the New Zealand school curriculum? 4) To critically engage and expand discussions of Niue literary landscapes between Niue and Māori, other Realm nations, and broader global Indigenous literary spaces.