Search Marsden awards 2008–2017

Recipient(s): Dr KP Ireton | PI | University of Otago

Public Summary: Many microbial pathogens actively promote their spreading from infected human cells to surrounding cells. Overall, spreading mechanisms are not well understood. The bacterial pathogen Listeria monocytogenes is an important cause of food-borne illnesses in humans and animals. Cell-cell spread of Listeria in the host intestinal epithelium is likely critical for disease. Our recent findings indicate that Listeria spreads through a novel process involving dissipation of tension at cell junctions. Listeria perturbs these junctions through a virulence factor called InlC. Our proposed research will test the hypothesis that InlC affects junctions and Listeria spreading by binding the human protein Sec31A, thereby interfering with protein trafficking from the endoplasmic reticulum to the Golgi. This work will provide novel insights on how pathogens spread, and may identify new pathways regulating cell junctions.

Recipient(s): Dr JM O'Sulllivan | PI | Massey University
Prof SM Gasser | AI | Friedrich Miescher Institute for Biomedical Research
Dr LR Gehlan | AI | Massey University
Dr MB Jones | AI | Massey University
Prof J Langowski | AI | German Cancer Research Centre
Prof RA Martienssen | AI | Cold Spring Harbor Laboratory

Public Summary: We can now sequence entire genomes within days. Moreover, it is possible to synthesize a genome and insert it into donor cells to form “synthetic” organisms. Despite these advances we have little understanding of the inter-relationships between genome structure and function. This is exemplified by our awareness that yeast cells have a position-based genetic memory, yet we remain unsure how this system relates to overall yeast genome structure. Our objective is to use Baker’s and fission yeast to investigate this inter-relationship and answer fundamental questions about the formation and inheritance of genome structure. We will integrate cutting-edge molecular and microscopic techniques to determine genome structure in synchronized yeast strains containing loci whose positions have been artificially constrained. Moreover, mutations within the fission yeast cell cycle and RNAi pathways will be used to resolve how chromatin organization is inherited. Our unique approach will shift the conceptual framework within which we consider three-dimensional genome structure and gene regulation. This will impact on a wide range of endeavours including our ability to predict how genetic modifications affect genome function in biotechnological and therapeutic applications. New Zealand will benefit through the development and repatriation of novel molecular, microscopic, bioinformatic and biophysical techniques.

Recipient(s): Assoc Prof K Witten | PI | Massey University
Prof R Kearns | PI | The University of Auckland
Dr L Asiasiga | AI | Massey University
Dr E Lin | AI | Massey University
Ms S Mavoa | AI | Massey University
Assoc Prof H Moewaka Barnes | AI | Massey University

Public Summary: The number of families with children living in intensive urban environments in Aotearoa/New Zealand has greatly increased in the past decade. This trend is likely to continue given housing affordability issues, rising transport costs, and nation-wide policies of urban intensification. Opportunities for outdoor play and independent mobility have been shown to effect children’s healthy cognitive, social and physical development. Yet lack of children’s outdoor amenities and an overwhelming emphasis on safety has resulted in a generation of urban children increasingly oriented to ‘the great indoors’, closely supervised while outside, and chauffeured to school and other activities by parents.

The aim of this project is to understand opportunities and constraints on play and independent activity for children living in medium and high density housing in inner city Auckland. It will investigate the mobility of children (8-11years) using Geographic Positioning and Information Systems (GPS and GIS); and, through one-on-one interviews, examine and contrast children’s and parents’ discourses and practices around play, safety, the built environment and wellbeing. Focus groups of parents and children will then consider how intensive urban environments could best support children’s safety and independent mobility, and the potential contributions of these for healthy child development.

Recipient(s): Dr HL Pham | PI | Victoria University of Wellington
Prof HG Dales | AI | University of Leeds

Public Summary: Banach spaces and Banach algebras are infinite-dimensional generalization of matrices. One source of inspiration for Banach spaces and Banach algebras is from the study of differential/integral operators. Group algebras and Fourier algebras of locally compact groups are special Banach algebras that model the well-known Fourier transformation. Cohomology theory provides a method of studying a particular algebra by studying a set of invariants called cohomology groups.

This project aims to resolve some natural questions in the cohomology theory of Banach algebras. Specifically, we aim to determine when certain natural modules over Fourier algebras satisfy certain homological properties. We plan to employ multi-Banach algebra techniques in attacking these questions. Multi-Banach algebras were introduced recently by Dales and Polyakov. Multi-norm techniques have proved to be a fruitful in solving problems in classical Banach algebra theory, as demonstrated in our recent work. We shall need to develop these techniques further in order to solve our current problems. We believe that our results will have important applications in other problems in Banach algebra theory outside those addressed in our project.

Recipient(s): Dr BC Monk | PI | University of Otago
Dr DS Bellows | AI | Victoria University of Wellington
Dr E Fleischer | AI | MicroCombiChem
Prof A Goffeau | AI | Universite catholique de Louvain
Dr MV Keniya | AI | University of Otago
Dr A Klinger | AI | MicroCombiChem
Dr RM Stroud | AI | University of California, San Francisco
Dr JDR Tyndall | AI | University of Otago

Public Summary: The induction of drug efflux pumps by xenobiotics has rendered useless many drugs and agrochemicals. A regulatory network that senses xenobiotics and confers multiple drug resistance on the model yeast Saccharomyces cerevisiae will be used to obtain proof-of-principle for multifunctional triazoles (MFTs). These compounds will be single molecule inhibitors of ergosterol biosynthesis and xenobiotic-induced multidrug efflux. We will seek compounds that inactivate a xenobiotic sensing transcriptional regulator which activates the Pleiotropic Drug Resistance network responsible for the efflux of azole antifungals. These transcriptional inactivators will be linked covalently to a triazole scaffold to test the MFT concept. MFTs will inhibit the triazole target (lanosterol 14alpha-demethylase), the transcriptional regulator (Pdr1p) and basal drug efflux by the pumps (e.g. the multidrug transporter Pdr5p) that remains after transcriptional inactivation. The fungistatic triazole drugs will also be rendered fungicidal. Structural resolution of the target molecules will assist in silico aspects of the drug discovery process. Our expertise in structural biology, yeast genetics, molecular modeling, drug screening, compound synthesis and medicinal chemistry, plus yeast resources unique to New Zealand, will be used to probe transcriptional modulation and develop a novel fungicidal chemotherapy that will lead to important applications in medicine and agriculture.

Recipient(s): Dr M Ehrgott | PI | The University of Auckland
Dr A Raith | AI | The University of Auckland
Dr JYT Wang | AI | The University of Auckland

Public Summary: We are surrounded by network structures. Everyone interacts with telecommunication, transportation and energy networks everyday. Mathematical models of these physical as well as many virtual networks representing the interactions between agents in an economy can be used to predict the behaviour of the agents in the networks and hence the performance of the networks. In this research, we are interested in equilibrium problems in networks. An equilibrium in a network is a state in which no agent has an incentive to change their own behaviour, because no such change results in an improvement of their situation. Existing theory assumes that agents use a single measure of cost or benefit to assess their situation, which is unrealistic. We investigate the more general and more realistic situation where cost and/or benefit is expressed through several incommensurate and conflicting objectives. Under this assumption, there exist multiple equilibria, and in our research we develop algorithms to find these multiple equilibria, study their mathematical properties, and their relevance in specific network types, thereby enriching the theoretical foundation of fields such as economics, transportation, supply chains, and finance.

Recipient(s): Prof R Hannah | PI | University of Otago
Dr E Boutsikas | PI | University of Kent

Public Summary: This project aims to investigate the relationships between astronomy and religion in ancient Greece. It seeks to do this via an analysis of aetiological myths, cult rituals and sacred buildings set within their surrounding terrestrial and celestial landscape, in mainland, western and eastern Greece.

A traditional role of observational astronomy in ancient Greece was to provide indications of pivotal moments of change in the agricultural year. These periods were in turn reflected in annual festivals in the calendar, celebrated at sanctuaries situated in a terrestrial and a celestial landscape. This project will argue that astronomy, myth, the content and timing of religious cult, and landscape in its totality all combine to provide a richer understanding of ancient science in its cultural context, and indeed of the interplay between science and religion in ancient Greece.

This project innovatively uses astronomy as a methodological tool to help elucidate and
explain Greek religious belief and practice. It will result in establishing a new, interdisciplinary methodology to the study of Greek religion, adaptable to other sites and cultures.

Recipient(s): Dr CM Larsen | PI | University of Otago

Public Summary: There is an increased incidence of mood disorders postpartum. Pathological anxiety, the most common, can have serious long-lasting consequences for mother and child. However, the lack of an appropriate animal model has impeded understanding of the mechanisms underlying this disorder. We have developed a unique rodent model of postpartum anxiety and have established that low prolactin in early pregnancy decreases neurogenesis in the subventricular zone (SVZ), adjacent to the lateral ventricles of the brain. Both low prolactin, and the associated decrease in SVZ neurogenesis, caused impaired maternal behavior and anxiety postpartum. This established for the first time a role for SVZ neurogenesis in mood and behavior. Using this model, we will now determine how prolactin stimulates neurogenesis, where the new neurons go and how they affect behavior, and whether increasing neurogenesis during pregnancy through dietary modifications or an increase in exercise can prevent postpartum anxiety. Further understanding of this debilitating illness will lead to new strategies to prevent the detrimental consequences for women, infants, and their families.

Recipient(s): Prof PJ Steel | PI | University of Canterbury
Prof FR Keene | PI | James Cook University

Public Summary: Modern material science and nanotechnology routinely exploit the properties of materials that contain metal atoms linked by organic molecules (ligands). We intend to dispel the current dogma that the best such bridging ligands use nitrogen heterocycles and carboxylic acids to bind the metal. Indeed, we contend that many hitherto overlooked interactions of organic functional groups with metal atoms can be harnessed to provide new building blocks for preparing both discrete and polymeric supramolecular assemblies. In this context, we will synthesise a diverse range of new bridging ligands that will be combined with various metals to assemble nanoscale species with defined architectures. By strategic design of these ligands and the appropriate choice of metal atoms we expect to prepare many new compounds that will have useful applications as functional materials, such as catalysts, sensors and multiple electron transfer agents. Examples will include 1D-coordination polymers, 2D-networks, 3D-frameworks (MOFs) and discrete assemblies such as molecular cages and helicates. Novel chiral and mixed-metal assemblies will also be studied and applications of these assemblies in organic synthesis will be investigated.

Recipient(s): Prof MJ Anderson | PI | Massey University
Prof KR Clarke | AI | Plymouth Marine Laboratory

Public Summary: Imagine sampling two communities of butterflies and asking: do they differ? Testing for a (mean) difference is not possible if one community is more variable than the other. For a single measurement (e.g. community diversity), this is ‘Behrens-Fisher’, one of the oldest problems in statistics. We will combine bootstrapping methods with distance-based tests, avoiding classical assumptions, to yield novel robust solutions to the multivariate (multi-species) Behrens-Fisher problem. This work will generate new possibilities for simultaneous inferences on means and variances in ecology. More broadly, it will crack current barriers to analysing any multivariate dataset where classical approaches fail.