Search Marsden awards 2008–2017
Search awarded Marsden Fund grants 2008–2017
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2010
Title: A new mechanism for post-transcriptional regulation in prokaryotes
Recipient(s): Assoc Prof VL Arcus | PI | University of Waikato
Dr R Colangeli | PI | University of Medicine and Dentistry of New Jersey
Public Summary: Many bacteria encounter dramatic changes in their environment during the course of their lifecycle. For example, the pathogen Mycobacterium tuberculosis (which causes tuberculosis) happily grows in complex, rich media. After infection, M. tuberculosis grows inside human immune cells called macrophages, where the bacteria are under attack – there is very little oxygen and the pH is unusually low. To survive in these very different environments, the bacterium must tightly tune its metabolism and growth to suit the conditions. New results from our laboratory, suggest that the “VapC” proteins control particular metabolic pathways in response to changes in the environment. They do this by targeting subsets of mRNA transcripts for degradation under certain environmental conditions. This provides a fast, concerted down-regulation of particular metabolic pathways, and represents a new mechanism for post-transcriptional regulation in prokaryotes. Our hypothesis is that VapC-mediated mRNA regulation is a general phenomenon as we have preliminary evidence that VapC proteins from opposite sides of the tree of life may have similar functions. VapC proteins are found in half of all bacteria and archaea. To test our hypothesis, we propose a range of biochemical and microbiological experiments using VapC proteins from a diverse range of bacteria and archaea.
Total Awarded: $778,305
Duration: 3
Host: University of Waikato
Contact Person: Assoc Prof VL Arcus
Panel: CMP
Project ID: 10-UOW-091
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2016
Title: A new paradigm for organelle targeting
Recipient(s): Professor AJ Fairbanks | PI | University of Canterbury
Dr AG Miller | AI | University of Canterbury
Professor FM Platt | AI | University of Oxford
Professor M Sollogoub | AI | Universite Pierre et Marie Curie (Univ Paris 6)
Public Summary: This innovative research program will develop a technology platform to target therapeutic agents to a specific cellular organelle: the lysosome. The ability to specifically deliver drug molecules to the lysosome is essential for the development of new and improved therapies for a range of >50 currently incurable diseases, including the lysosomal storage disorders.
We will target a cellular receptor that internalises molecules that carry a specific carbohydrate tag, called mannose-6-phosphate (M6P), and then delivers them to the lysosome. The precise attachment of M6P-tags to therapeutic agents will mean that they are trafficked by this receptor’s action, and so represents a highly specific way of targeting them to the lysosome.
We will develop a unique method to attach M6P-targeting tags to bioactive agents in a completely controlled fashion, using world-leading synthetic chemistry and biocatalysis. Exquisitely selective synthesis will produce M6P-tags with optimal structure for processing by the receptor. Enzyme engineering will produce biocatalysts that irreversibly attach these tags to bioactive molecules. In vitro cellular imaging studies will then demonstrate that the M6P-tagged bioactives are efficiently transported to the lysosome. Realisation of our approach will enable the development of new lysosomal-targeted therapies, and the potential treatment of >50 incurable diseases.
Total Awarded: $870,000
Duration: 3
Host: University of Canterbury
Contact Person: Professor AJ Fairbanks
Panel: PCB
Project ID: 16-UOC-009
Fund Type: Marsden Fund
Category: Fast-Start
Year Awarded: 2009
Title: A new paradigm of medieval literary anonymity
Recipient(s): Dr SC Marshall | PI | University of Otago
Public Summary: In this project, I plan to establish a new paradigm of anonymity in medieval literature. Most scholars assume that medieval anonymity resulted from a lack of authorial individualism, but by investigating different types of anonymity in medieval texts, I argue that such a notion is simplistic. Instead I suggest that anonymity is a complex and conscious feature of medieval authorship. Positioning anonymity as a literary convention with an extensive history will substantially revise scholarly attitudes by broadening research into authorship, canon formation, and the reception history of medieval literature.
Total Awarded: $201,778
Duration: 3
Host: University of Otago
Contact Person: Dr SC Marshall
Panel: HUM
Project ID: 09-UOO-005
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2014
Title: A new politics of peace? Investigations in contemporary pacifism and nonviolence
Recipient(s): Professor RDW Jackson | PI | University of Otago
Dr JM Moses | AI | University of Canterbury
Public Summary: Pacifism and nonviolence can be a highly successful and viable approach to political reform, and has the potential to form the basis for civilian national defence, nonviolent peacekeeping and a peaceful political order. Yet, few scholars have attempted to understand the discursive and theoretical basis of public, political and academic understandings of nonviolence and pacifism, or its consequences for policies related to national defence and war, international relations, war memorialisation and political culture more generally. This study is the first systematic exploration of the social, political and academic discourses of nonviolence and pacifism, and the nature and consequences of its current status as a form of ‘subjugated knowledge’ in contemporary society. It will offer new insights and understanding of why nonviolence and pacifism remains a form of subjugated knowledge, despite its well-documented successes, and fill an important research gap in the current literature on nonviolent movements. More importantly, it will have genuine normative potential for peace workers seeking to transform violent cultures and build positive peace, indigenous communities seeking to de-subjugate traditional forms of knowledge, and scholars and practitioners of international relations and foreign policy seeking to reintroduce pacifism as a legitimate form of political theory into international politics.
Total Awarded: $595,000
Duration: 3
Host: University of Otago
Contact Person: Professor RDW Jackson
Panel: SOC
Project ID: 14-UOO-075
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2017
Title: A new role for HDAC4 in neuronal morphogenesis and memory
Recipient(s): Dr HL Fitzsimons | PI | Massey University Manawatu
Dr D Wheeler | AI | Massey University Manawatu
Public Summary: Impaired function of the histone deacetylase HDAC4 has been found in several neurodevelopmental and neurodegenerative disorders that are associated with cognitive impairments, and we have recently shown that HDAC4 plays a critical role in both long-term memory formation and neuronal development in Drosophila. HDACs are classically known to act in the nucleus of the cell to regulate gene expression; however HDAC4 is predominantly non-nuclear in neurons. Despite this, investigation of the non-nuclear functions of HDAC4 has been largely overlooked. In a recent breakthrough, we discovered that HDAC4 interacts genetically with a cluster of genes that regulate the actin cytoskeleton, a structure that allows a cell to grow and move. This is an exciting finding given that both memory formation and neuronal morphogenesis are dependent on remodeling of the actin cytoskeleton. Here, we propose to investigate the nuclear and non-nuclear roles of HDAC4 in memory and neuronal morphogenesis by investigating the mechanisms through which it interacts with cytoskeletal regulators that modulate these processes. Our Drosophila model is extremely powerful for neuroscientific discovery as it provides the ability to combine genetic, biochemical and behavioural analyses in the same in vivo system and thus is ideally suited to gaining insights into HDAC4 function.
Total Awarded: $795,000
Duration: 3
Host: Massey University Manawatu
Contact Person: Dr HL Fitzsimons
Panel: CMP
Project ID: 17-MAU-119
Fund Type: Marsden Fund
Category: Fast-Start
Year Awarded: 2012
Title: A new solution to a perennial problem: resolving a paradox in pursuit of ecology's Holy Grail
Recipient(s): Dr DC Laughlin | PI | University of Waikato
Public Summary: The potential of predicting species abundances using physiological principles has generated tremendous interest, inspired vigorous debate, and has been heralded as the Holy Grail of Ecology. However, assembly theory is haunted by a paradox: environmental filtering tends to increase the functional similarity of species within communities leading to trait convergence, whereas competition tends to limit the functional similarity of species within communities leading to trait divergence. I have developed a new mathematical approach that resolves these paradoxical predictions within a Bayesian framework by incorporating intraspecific trait variation. This model unifies evolutionary biology with community ecology and makes assembly theory potentially falsifiable. The framework is generalizable to any ecosystem as it can accommodate any species pool, any set of functional traits, and multiple environmental gradients, and it eliminates some of the criticisms associated with recent modeling approaches. This project will test the predictions of assembly theory along two distinct environmental gradients: at the local scale along a strong soil nutrient gradient, and at the national scale along a broad climatic gradient. The model is founded on general biological principles and may improve our ability to predict species abundances across multiple taxa in any ecosystem on the planet.
Total Awarded: $300,000
Duration: 3
Host: University of Waikato
Contact Person: Dr DC Laughlin
Panel: EEB
Project ID: 12-UOW-041
Fund Type: Marsden Fund
Category: Fast-Start
Year Awarded: 2010
Title: A novel approach for probing unsteady boundary layer separation
Recipient(s): Dr RJ Clarke | PI | The University of Auckland
Assoc Prof JP Denier | AI | The University of Adelaide
Dr RE Hewitt | AI | University of Manchester
Public Summary: Understanding how boundary layers, thin regions of high shear which form on surfaces in fast moving flow, become detached in a time-dependent manner remains one of the great challenges in fluid dynamics. Such separations are commonplace, and often drastically alter the character of a flow. Hence, discerning their nature offers huge rewards across a diverse range of areas, extending from turbulent transitions, to improved models of fluid mechanics in the human body. The proposed PI and international colleagues recently prototyped a novel benchtop experiment that can shed light on this important mechanism. Data obtained from preliminary investigations hints at phenomena predicted by current unsteady separation theories, as well as uncovering a rich array of flow behaviours yet to be fully understood. The research program proposed here sets out to build upon these initial successes, and realise the full potential of this experimental regime. A blend of extensive flow measurements, sophisticated simulations, and advanced theoretical techniques will be employed to deepen our appreciation of this fundamental and pervasive process. Connections between unsteady separation and flow instabilities will be explored, as will the role of centrifugal effects. The ultimate state of decaying turbulence, often realized experiments, will also be of intense interest.
Total Awarded: $260,870
Duration: 3
Host: The University of Auckland
Contact Person: Dr RJ Clarke
Panel: EIS
Project ID: 10-UOA-083
Fund Type: Marsden Fund
Category: Fast-Start
Year Awarded: 2015
Title: A novel approach for studying the mechanoenergetics of the heart at the tissue level
Recipient(s): Dr J-C Han | PI | The University of Auckland
Associate Professor AJ Taberner | AI | The University of Auckland
Associate Professor DS Loiselle | AI | The University of Auckland
Public Summary: The geometry of the heart is extremely complex. For that reason, exploration and understanding of its performance has relied heavily on experiments using tissues isolated from its ventricles. However, current experimental methods do not expose isolated tissues to the same contraction pattern as naturally experienced by the heart. Specifically, the mechanics of the heart when it ejects blood is not mimicked in tissue experiments. This limitation may explain why some tissue performance appears inconsistent with that of the heart. It has also constrained the use of isolated tissue to study heart failure.
To better understand cardiac muscle function in health and disease, we propose to develop, using our unique instrument, a contraction protocol for isolated tissues that describes the interaction between the ventricles and the arterial system during ejection. This new protocol realistically mimics the ejection pattern of the heart, and will enable entirely new questions to be answered in future isolated cardiac tissues studies. For this project, we will use the new protocol to resolve fundamental organ-tissue puzzles in cardiac research, and to characterise the performance of tissues isolated from rat hearts suffering impaired ejection, thereby gaining insight into the detrimental effects of elevated blood pressure on cardiac function.
Total Awarded: $300,000
Duration: 3
Host: The University of Auckland
Contact Person: Dr J-C Han
Panel: BMS
Project ID: 15-UOA-209
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2015
Title: A novel molecular sensor to optimise central nervous system gene therapy
Recipient(s): Associate Professor DS Young | PI | The University of Auckland
Dr AI Mouravlev | AI | The University of Auckland
Public Summary: Gene therapy is at the forefront of medical technologies with the potential to effectively treat chronic neurodegenerative diseases. An inability to selectively restrict the therapy to sick cells, leaving healthy cells unaffected, is a key barrier to broader translation of this technology from the bench to the clinic. We have designed a novel gene regulation system that relies on cell stress to selectively switch on expression of a therapeutic gene in at-risk cells only for use in gene therapy. The aim of this project is to refine the ARF5 switch used in our gene regulation system, and validate the functionality of our system in driving production of therapeutic artificial microRNA (miR) sequences that mediate gene silencing, or a gene cocktail that enables simultaneous therapeutic intervention at different biochemical pathways. Animal and cell models of Huntington's disease will be used in proof-of-concept studies to determine whether regulated production of artificial mIR sequences targeting a pathogenic mutant huntingtin gene alone or in combination with a brain-derived neurotrophic factor transgene can effectively ameliorate neuropathology and behavioural deficits. The outcomes of this research address an unmet need for cutting-edge technological advancements that will increase the specificity and safety of gene therapy for human application.
Total Awarded: $840,000
Duration: 3
Host: The University of Auckland
Contact Person: Associate Professor DS Young
Panel: BMS
Project ID: 15-UOA-039
Fund Type: Marsden Fund
Category: Standard
Year Awarded: 2011
Title: A novel route to restricting G-protein coupled receptor signalling
Recipient(s): Assoc Prof M Glass | PI | The University of Auckland
Dr DP Furkert | AI | The University of Auckland
Dr JK Northup | AI | National Institute on Deafness and Other Communication Disorders
Assoc Prof KD Pfleger | AI | Western Australian Institute for Medical Research
Public Summary: Almost half of all the medicines we currently use work on just one type of drug target, known as G-protein coupled receptors (GPCRs). These are molecular complexes which allow cells to communicate with each other. There are many different types of GPCR. Each is spread widely throughout the body and controls many cellular processes.
As drug targets, GPCRs can be difficult to predict and may produce adverse drug effects. The medicine may act on undesirable cellular pathways, or on cells in regions of the brain or body that are quite distinct from the areas which produce the desired therapeutic effect.
This project will examine ways to specifically target the required GPCRs and minimise unwanted drug effects. The latest research shows GPCRs can combine to form complexes with other types of GPCRs. These complexes combine to produce their own effects, independent of their constituent parts. By targeting two receptors, it’s possible to increase the likelihood the drug will activate the correct subset of receptors, as well as forcing the receptor complex to interact with specific signalling molecules. This project aims to develop a greater understanding of one specific receptor complex and use this to develop drugs with less adverse effects.
Total Awarded: $782,609
Duration: 3
Host: The University of Auckland
Contact Person: Assoc Prof M Glass
Panel: BMS
Project ID: 11-UOA-201