Search Rutherford Discovery Fellowship awards 2010–2017

Public Summary: Funding not taken up

Public Summary: The early stages of pregnancy are a critical time, as the developing fetus establishes mechanisms to exchange nutrients and waste with its mother. Any problems in this process can lead to miscarriage, developmental problems, and even health problems in later life. Risk factors have been identified that appear to contribute to problems in early pregnancy such as genetics or maternal health issues. However, to improve management of at risk pregnancies we need to understand more about how and why problems can occur. A major issue in identifying the causes of problems in early pregnancy is that many techniques that would usually be used to monitor health issues cannot be used in pregnancy, so descriptions of normal and abnormal development are made from ‘low-resolution’ observations. For example, high-resolution images are often helpful to diagnose disease and to understand the mechanisms that lead to ill health, but the most advanced imaging technologies (like CT) are not always considered safe in pregnancy. Therefore, we rely mainly on ultrasound to observe health in pregnancy, which allows us to see many important features of the developing fetus, but is not as sensitive to small changes in developing blood vessels or organs as other modern imaging techniques. By using computational techniques and mathematics that describe the physical processes occurring in early pregnancy I plan to provide a framework that can fill the gaps between observations made by scientists working in different disciplines, from cell biologists to ultrasound specialists. This will allow us to build a more complete picture of the mechanisms that drive early development of the placenta and fetus. Ultimately, this will provide new ways to develop markers of risk by providing an interpretation of how potential markers can affect developmental processes and to allow us to better assess how subtle differences in function can lead to different outcomes in terms of child and maternal health.

Public Summary: Cooperation is critical to surviving and thriving in human societies; yet humans vary in their cooperative inclinations and, as a result, cooperation is difficult to sustain. Why are some people more likely to cooperate than others? The proposed research will address this important question by identifying how two contexts of early experience, culture and caregiver interactions, shape the development of cooperation in early childhood. Project 1 will examine whether there are cross-cultural differences in young children’s cooperation understanding, ability and motivation. By comparing the cooperative tendencies of children being raised in New Zealand to those of children being raised in Vanuatu. This project will demonstrate for the first time whether the variability that has been found across cultures in adults’ cooperative behaviour is evident in the earliest forms of cooperation in which humans engage, or whether such differences only emerge through years of socialization within one’s cultural context. Project 2 will identify the communicative foundations of cooperation by: 1) developing and validating the world’s first virtual infant model, BabyX, which will be able to simulate infants’ interactive behaviour, and 2) using BabyX to test how discrete changes in infants’ behaviour influence the cooperative nature of early interactions. To validate this new research tool, experiments will be conducted in which parents will interact with BabyX in a “virtual interaction swap” to test the model’s ability to elicit responses consistent with how parents interact with their own babies in an observational setting. After validation, further experiments will be conducted in which BabyX’s cooperative behaviour during the interaction will be manipulated in systematic ways (e.g. responds to caregiver with smiles and eye contact or responds with a frown and no eye gaze) to test which features of behaviour give rise to coordinated interactions. This will be the first demonstration of how specific features of infant behaviour disrupt (or enhance) the cooperative nature of their early caregiver interactions. My Rutherford research programme will provide novel insights into how two important forms of experience, culture and early infant-caregiver interactions, shape cooperation in early childhood. By bringing together two distinct methodologies under one research programme, this research will provide the first integrated model revealing how the diverse range of early experiences faced by children shape cooperation development. The results will advance science by enhancing theories of human cooperation, pro-social development, and wil contribute to the creation of tools to promote cooperation in early childhood. The thought and behaviour patterns that are established in the first few years of life have profound consequences throughout life. Thus, isolating the factors that promote cooperation early in life is key to enhancing human cooperative tendencies throughout development.

Public Summary: Although our memories play like movies in our minds, memories are stored very differently in our brains. The various details of memories are stored as fragments in different brain areas and memories are then reconstructed when we remember. The hippocampus is a critical brain region in this constructive process; it locates and reintegrates the details comprising a memory. One downside of reconstructing memories is that memory errors called conjunction errors can occur; details from two memories may be mixed into one memory. Recent work has shown that storing memories in fragments does have advantages: these details can be used to imagine novel future events. Neuroimaging has revealed that the hippocampus is involved not only in reconstructing memories of past events but also constructing future events. The proposed research will extend these findings in three novel directions: (1) to determine whether the hippocampus is involved in conjunction errors when retrieving autobiographical memories; (2) to determine whether different parts of the hippocampus play distinct roles in future imagination; (3) to investigate how hippocampal dysfunction in depression impairs the ability to construct memories and future events. This programme will therefore advance our understanding of the role of the hippocampus in constructive memory processes.

Public Summary: I will develop computational tools to improve our understanding of the processes that generate Earth's biodiversity, past, present and future. Questions such as how species evolve in the face of infectious disease and climate change still demand satisfactory answers. I will lead an international collaborative project to develop novel computational models to shed light on the processes of speciation, diversification and extinction. In particular, I will develop automatic methods for estimating species delimitation and relationships by combining genomic and ecological data. I will also unify ecological niche modeling with statistical phylogeography to facilitate prediction of future species distributions and survival. To understand the origins and maintenance of biodiversity requires a statistical framework that can synthesize molecular data with ecology and climate, producing a comprehensive picture of the historical origins of biodiversity and uncovering the environmental drivers of ecosystems and their constituent species. Finally I will unify mathematical epidemiology and viral phylogenetics, creating methods to predict epidemic outcomes from sequence-based surveillance data. Overall I aim to untangle the contributions of historical contingency and environment to the maintenance of biodiversity and I will develop software and models to analyze phylogeographic, ecological and climatic data to address a broad range of evolutionary questions.

Public Summary: The ability to integrate new genomic technologies with sophisticated computational analysis remains a key bottleneck in advancing the biological sciences. The interdisciplinary field of computational genomics is increasingly linking these diverse subject areas. My research program leverages national and international connections to address outstanding biological questions at this interface of genomics, computer science and statistics. Here, I focus on two related areas of research: demographic inference and genome evolution. Firstly, I propose to infer human prehistory in the Pacific using high throughput genome sequencing to target and sequence multiple neutral regions from across the human genome. I will reconstruct the history of human populations in my specialist area, the Indo-Pacific region, which has traditionally been ignored by large sequencing initiatives. Secondly, I propose to dissect the evolutionary basis of gene regulation in an inter-species fungal hybrid. Fungi are important for insect biocontrol in New Zealand's pasture grasses. One such strain derives from highly divergent parent species. I will sequence transcriptomes of both the hybrid and its parents to identify how gene expression is regulated when genomes from two very different progenitors merge. This composite research program will advance New Zealand's capability in computational genomics.

Public Summary: Islands comprise only 5% of the world’s land area, but contain over 20% of the world’s biodiversity, and have experienced over half of recent species extinctions. Invasive species are the number one threat to islands, and New Zealand has already lost 40% of its native land birds. However, New Zealand has also led the world in developing innovative tools for managing invasive pests, having eliminated introduced mammals from over 100 uninhabited islands, increasing pest-free island estate from 0.5 to 10%. In 2014 we celebrate 50 years of rodent eradications in New Zealand, and for the next 50 years a vision for a Predator-Free New Zealand has been identified. However, the path ahead has many challenges, with only 0.25% of New Zealand’s ‘mainland’ (North & South islands) currently receiving meaningful pest control. In order to scale predator control up across New Zealand’s largest islands (Great Barrier, Stewart, North and South) research must directly tackle critical knowledge deficiencies in 1) behaviour of pests at low densities, 2) surprise effects among multiple pest species, 3) prioritising and optimising allocation of pest control resources, and 4) public attitudes to pest species and their control. Only by addressing these knowledge gaps with a unified research programme leveraging ‘stepping-stone’ achievements will it be possible to realise the aspirations of a Predator-Free New Zealand, and the economic and environmental benefits this will bring. Three contrasting sites will be used as the stepping-stone lynch pins of a five year research programme aimed at accelerating the pace of vertebrate pest control in New Zealand. Two of the sites will be islands, each with multiple interacting introduced mammal species, and one of these with a substantial resident human population. The third site is a ‘mainland island’ where pest control is being scaled to the mainland. At each site trapping, tracking, diet and genetic analyses will be used to develop a sound biological understanding of introduced species interactions, and their behaviour at low density under existing control. These results will be used to derive models of population dynamics, which can be applied to national pest control data now available for the first time in order to prioritise and optimise economies of scaling vertebrate pest control across much larger areas of New Zealand. Each site also contrasts in the nature of public engagement; one island privately owned by a small family, another island occupied by hundreds of residents, and the third mainland site drawing in volunteers from across a large urban metropolis. The differing environmental attitudes, conservation expectations, and conflicts of each group will be studied using both participatory and survey methods. The results of the research programme will be used to test hypothetical management scenarios in coupled socio-ecological systems, such as investing in ongoing mammal control or eradication, which tools are appropriate and acceptable for pest control, and the appropriate manner to engage with stakeholder groups. The knowledge generated will be used to co-produce with stakeholders a blueprint for conservation, and will create unifying methodological insights across the natural and social sciences.

Public Summary: In Aotearoa/New Zealand, calls for greater constitutional accommodation of Maori have been persistent since 1840. There are a myriad of justifications offered, including concern about the legitimacy of the New Zealand state given the lack of convincing legal or theoretical explanation for its formation and ongoing authority, the puzzle of how to reconcile state jurisdiction and recognition and accommodation of Maori authority, the need to ensure equality between Maori and non-Maori, including to ameliorate structural racism, and the ongoing impacts of economic, social and cultural marginalization of Maori. The political and legal appetite for constitutional transformation appears to be growing, supported by the government-initiated Constitutional Advisory Panel’s Report on New Zealand’s Constitution (2013). In 2016 Andrew Butler and Geoffrey Palmer published A Constitution for Aotearoa/New Zealand, recommending that Te Tiriti o Waitangi to be recognized and affirmed, which is stimulating a wider public discussion. Of especial moment, the Iwi Chairs’ Independent Working Group on Constitutional Change, Matike Mai Aotearoa, recently published its report on Maori visions for New Zealand’s Constitution, based on many years of research, especially at the flax-roots level. In my keynote address for the New Zealand Law Commission’s 30th Anniversary, drawing on scholarship over decades, I argued that constitutional transformation in the form of greater accommodation of tino rangatiratanga is needed to legitimize the New Zealand. New Zealand is not alone. There have been recent and/or are ongoing attempts to provide greater recognition and accommodation of Indigenous peoples under domestic, often times constitutional, law around the globe. In many cases, developments have been inspired and supported by the UN Declaration on the Rights of Indigenous Peoples (Indigenous Declaration), adopted by the General Assembly in 2007, and ongoing international oversight of states’ actions with respect to Indigenous peoples. They also reflect a shift in focus back to the domestic after decades of movement at the international level. More normatively, they evidence an appreciation that Indigenous peoples should be accommodated in the constituting laws of the state. However, states and Indigenous peoples have and continue to face questions about the “how”. What might be the best means to accommodate Indigenous peoples’ claims and rights? What options are on the table? What works? How do we move from broad and principled objective to practical and effective legal tools? How might a constitution fairly balance Indigenous peoples’ rights and non-Indigenous peoples’ rights? I propose to evaluate various existing and proposed methods of constitutionally recognizing and accommodating Indigenous peoples’ rights around the globe with a view to informing potential reform in Aotearoa. I propose to consider for inclusion: Mexico’s recognition of Indigenous autonomy and international treaties setting out Indigenous peoples’ rights; Bolivia’s constitutional reform including incorporation of the UN Indigenous Declaration; Australia’s current attempt to recognise Indigenous peoples in its Constitution; recognition of customary law in Pacific constitutions and the South African Constitution; Norway, Finland and Sweden’s establishment of Sami Parliaments and the development of a Nordic Sami Convention; Denmark’s home rule for Greenland; Canada’s constitution protection of treaty rights and Aboriginal rights; and the United States’ recognition of American Indian inherent sovereignty. I will be focusing on recognition of Indigenous jurisdiction and autonomy, protection of treaty and aboriginal rights, rights to lands, rights to culture and access to political power. I hope to provide pragmatic recommendations to illustrate how Indigenous peoples might be better constitutionally recognized, albeit taking into account the varied political, historical, economic and social

Public Summary: At the smallest functional scale, the living world is made up of tiny molecular machines that carry out all the functions essential for life. These molecules consist of collections of atoms glued together in particular arrangements. I am interested in how the structure and motion of these biological molecules determine how they function. Atoms are much too small to see even with the most sophisticated laboratory equipment, so I use computer simulations to follow how the atoms move – effectively, I make movies of molecules as they dance their way through life. To make these movies, rules that govern how the atoms interact with each other are needed, but these rules are only known for the most common biological molecules. This means that most computer simulations are of just one molecule, whereas in reality there are many different types of molecules crowded together. An important aspect of my research involves developing a way to automatically determine the rules for almost any molecule imaginable. This will enable simulation of molecules in realistic biological environments. For instance, I will investigate a protein that acts like a very specific molecular hoover: it first recognises and navigates to a particular part of the cell membrane, and once there, it neatly vacuums up only one kind of lipid molecule. We know that cancer-related changes to this protein make it hyperactive, but we do not know how they have this effect. My simulations will allow us to watch and compare how normal and cancerous versions of this protein do their job, and so help us to design anti-cancer drugs. Another of my research goals is to decipher the structure of proteins associated with the cell membrane, for which the usual structure determination methods do not work. Many of these proteins are existing or potential drug targets, so it is vital that we determine their structures as a first step towards rational drug design and improvement. I am developing ways of using the rules of atom behaviour from my simulations to help interpret data from one of the few experimental techniques that can be carried out on these proteins. I am also using computer simulations to investigate evolutionary relationships. These are usually determined by comparing genome sequences, but this fails at long evolutionary distances. Protein structures change much less over evolutionary time than sequences, however, so I am developing methods for inferring evolutionary relationships by comparing protein structures. I will use computer simulations to explore the different structures a particular protein can form, and so gauge the statistical significance of evolutionary distances. The different threads of my research programme are united by the use of computer simulations to make movies of molecules. If a picture is worth a thousand words, how much is a movie worth?

Public Summary: Diabetes is a growing epidemic in New Zealand and internationally, with an increased demand for new approaches for its prevention and treatment. But specific prevention and treatment approaches must be informed by sound knowledge of the metabolic pathways of diabetes. However, diabetes is not a single homogeneous disease but rather composed of several diseases with high blood sugar, or hyperglycaemia, as a common feature. Hence, the need for precise characterisation of the derangements of glucose homeostasis in various subsets of diabetes is being increasingly recognised. Dr Petrov will use his Rutherford Discovery Fellowship to investigate specifically the metabolic pathways underlying post-pancreatitis diabetes - the disease that currently affects up to 10,000 New Zealanders and its frequency is expected to rise considerably with the aging of the population in New Zealand. The objectives of this programme are designed to provide, for the first time, careful mechanistic investigations of the metabolic derangements of the exocrine and endocrine systems after pancreatitis to better understand mechanism and provide a pathway to prevention and treatment of post-pancreatitis diabetes. Given that diabetes drugs market is now a $100 billion industry worldwide (with a particularly strong growth in the East Asia and Pacific region), this programme will open up a great opportunity to explore the therapeutic potential of certain signaling molecules in the body as targets specifically for patients with post-pancreatitis diabetes. And this will lead to new employments in companies that manufacture diabetes drugs in New Zealand and have a potential to trigger interest of major pharmaceutical companies overseas. It will also contribute to New Zealand economy by reducing lost work days and early exit from the workforce of patients with diabetes. The social impact of this programme will include extending the life span of Maori people, who are disproportionately affected by post-pancreatitis diabetes. The indirect benefit of this programme will include scientific workforce development and raising the profile of the university and the country internationally.