Wednesday 3 November 2021 2:43pm
Professor Mark Hampton, Dr Mei Peng and Distinguished Professor Neil Gemmell are all recipients in the latest round of Marsden funding.
The secrets behind people’s food choices, ageing, and why some fish change sex, are set to be unlocked after Otago researchers secured $17.2 million in Marsden funding.
Twenty-three University of Otago “blue-sky” projects have received some of the $82.345 million allocated by Te Pūtea Rangahau a Marsden, The Marsden Fund, to 120 research projects throughout Aotearoa New Zealand.
Seventeen of the Otago studies received grants ranging from $660,000 to $960,000, and a further six researchers received kick-start $360,000 grants.
Deputy Vice-Chancellor, Research and Enterprise, Professor Richard Blaikie says it is excellent news that Otago’s researchers and research teams will be supported by Te Pūtea Rangahau a Marsden.
“These projects are at the forefront of advancing knowledge in their disciplines, led by many of our best established and emerging researchers,” Professor Blaikie says.
“Direct benefits to New Zealanders and New Zealand communities will come from many of these projects, with others strongly enhancing the body of knowledge upon which future developments will be built.”
Senior Lecturer in the Department of Food Science Dr Mei Peng says she is grateful to secure $839,000 for her research, which aims to find out whether there is a brain response guiding people’s food choices.
Her team will use pregnancy as a natural model to understand how the human brain adjusts to changing metabolic needs through food choices.
The Marsden funding will be used to develop a longitudinal project that will track a group of New Zealand women through the course of their pregnancies.
“This funding will help us answer what we think are interesting and important questions, provide training opportunities for several students and fund an early career researcher, none of which would be possible without this significant level of support.”
Dr Peng says her research will develop multidisciplinary skills that are necessary in addressing the global obesity epidemic and will help explain factors influencing postnatal health, therefore improving mothers’ psychological and physical wellbeing.
“As an early career researcher, receiving this full Marsden grant provides an amazing opportunity that allows me and my team to develop an exciting new program to tackle critical questions important for Aotearoa,” Dr Peng says.
Professor Mark Hampton, from the Department of Pathology and Biomedical Science, University of Otago Christchurch, secured $960,000 to investigate what happens in cells as people age.
He says he hopes to find out what controls how quickly red blood cells recover from oxidative stress and why it appears to differ between people.
Extending the lifetime of stored red blood cells would be valuable for improving the quality of blood used for transfusions. More broadly, changes in how red blood cells cope with oxidative stress may reflect what is happening in other cells in our body as we age.
Professor Hampton says understanding what happens in cells as people age will be important to help reduce the impact of age-related diseases.
“It is commonly believed that we know everything of interest about red blood cells. However, we have made some unusual observations about how they respond to stress. This project provides us with the opportunity to begin to search for answers,” he says.
This year’s Marsden funding will also help Distinguished Professor Neil Gemmell, from the Department of Anatomy, research “one of the most extra-ordinary transformations in nature”.
He received $926,000 to research why about 500 fish species undertake sex change as a normal part of their lives. It is a topic Dr Gemmell says he has been “fascinated” by after finding out about sex change in fish as a young boy fishing for spotties off the wharves in Wellington.
“I was amazed to discover that the humble spotties I was catching were one of the species that starts out life as female and changes sex to male later in life. Fast forward some decades and I am now using spotties as a model to understand how exactly this process is initiated.”
Dr Gemmell says he feels fortunate to secure the funding.
“This funding will help us answer what we think are interesting and important questions, provide training opportunities for several students and fund an early career researcher, none of which would be possible without this significant level of support,” he says.
In announcing the awards today, Marsden Fund Council Chair Professor David Bilkey said Te Pūtea Rangahau a Marsden is designed to enable and create momentum for leading and up-and-coming researchers to develop their most innovative and ambitious ideas.
“This support of fundamental ‘blue-sky’ research is crucial to ensuring a healthy, vibrant and resilient research culture in Aotearoa, capable of addressing major societal challenges, as we have seen recently with the response to the COVID-19 pandemic,” Professor Bilkey says.
“The range of knowledge represented in this year’s funded research is something to be proud of, with research excellence and scholarly impact in areas such as hauora health, climate, and languages.”
The successful recipients are:
Professor Robert Poulin, Zoology
Parasite microbiomes and host manipulation: who’s really pulling the strings?
The microbiome revolution sweeping through evolutionary biology has replaced the concept of ‘organism’ with the holobiont, in which animals and their associated microbes form integrated entities. Parasites have their own microbes, which may assist them in exploiting their host, possibly even in usurping host behaviour for the parasites’ benefit. We will test the hypothesis that the parasite microbiota plays a key role in modulating the extent to which the host behavioural phenotype is manipulated. Using three model systems consisting of native arthropods and their parasitic worms in which parasite-induced changes in host behaviour have been well documented, our research will use powerful tools including behavioural assays, metagenomic sequencing, metabolomic analyses and experimental alteration of parasite microbiota. Our innovative and multi-pronged approach will allow a thorough test of whether bacteria and viruses lurking within parasites are the real manipulators of host behaviour.
Associate Professor Priscilla Wehi, Centre for Sustainability
Kaitiakitanga and Antarctic narratives
Māori philosophical concepts like kaitiakitanga highlight the responsibilities we have to past, present, and future generations, as well as connections to place. We explore how kaitiakitanga operates at the edges of human experience, using Antarctica as a catalyst because of its physical remoteness, ephemeral human presence, and lack of sovereign governance. By examining kaitiakitanga in the context of extreme remoteness, we move closer to understanding its conceptual underpinnings, normative force, and potential for transformation. Our team of philosophers, scientists and artists will explore conceptual shifts that can both reveal and enable socio-environmental relationships that in turn begin charting a way to planetary wellbeing, with social and environmental justice at its centre. Together, we will learn about kaitiakitanga, its conceptual and physical boundaries, and potential applications in novel contexts, and create a visual repository of these knowledge shifts, within a mātauranga tradition of both ancient and innovative work that will be shown in a curated exhibition. Navigating the finite boundaries and infinite reach of Māori philosophical ideas, this project brings ancestral methodologies, from pūrakau (stories) through to traditional and contemporary visual and sensory transformations of Māori knowledge, to bear on the urgent need for future reimagining of human and planetary futures.
Dr Paul Szyszka, Zoology
The olfactory cocktail party: How animals and humans segregate mixed odours
Most animals rely on odours to locate food, mates, habitats, and dangers. Although odours from different sources mix, animals can segregate relevant odour sources. But how they solve this olfactory cocktail party problem is unknown. Insects use small time differences in odorant arrival to segregate odours from different sources. We will test the hypothesis that vertebrates, too, can segregate odours using temporal cues, and we will uncover the natural stimulus dynamics that enable odour source segregation. Revealing odour segregation processes in animals and humans has important implications for ecology (foraging), pest control (pheromone traps), scent-detection technology, and neurology (disease indicators).
Dr Rosie Brown, Physiology, School of Biomedical Sciences
Rewarding Mum: hormones supporting maternal-infant interactions
Motivation by a mother to engage in sustained nurturing behaviour is critical for the survival of offspring and the ongoing survival of a species. Changes in reward circuitry in a mother’s brain ensure interactions with newborn offspring are rewarding to a mother, however, the mechanism that simulates high levels of maternal motivation specifically in mothers is unknown. This project examines how hormones engage with the brain’s reward pathways to sustain a mother’s investment in caring for offspring. We will specifically test the hypothesis that the hormones prolactin and estrogen act on a population of neurons (galanin neurons) in a specific region of the brain, the medial preoptic area of the hypothalamus, to motivate mothers to care for young. We will utilise two recent technical developments to assess reward circuitry activity, and to determine the key hormonal signals and neuronal populations required for maternal motivation. This research will provide novel insights into how hormones alter motivation to fundamentally change behaviour in new mothers.
Associate Professor Peter Mace, Biochemistry, School of Biomedical Sciences
Reprogramming transcription with a flexible degradation machine
A cell must drastically change gene expression as it matures from a progenitor to a specific cell type. To change expression decisively, transcription factors are tagged with ubiquitin and ultimately degraded. Here we will investigate a central hub that tags transcription factors for degradation—the COP1 complex. In humans, COP1 regulates transcription factors that control development of many cell types, particularly metabolic, neuronal, and blood cells, and is linked to several disease states. We will determine how COP1 and its partners switch between degrading different transcription factors, aiming to understand how different mechanisms of COP1 function govern target degradation. We will also use engineered small antibodies, known as nanobodies, to disrupt the balance of COP1 activity and promote terminal differentiation of immune cells. Forcing terminal differentiation of pluripotent cells could form the basis of future disease therapy. Overall, this work will shed light on the fundamental question of how transcription factors are degraded during development and uncover ways to manipulate this process when it is disrupted in disease.
Distinguished Professor Neil Gemmell, Anatomy, School of Biomedical Sciences
Succession or suppression: how do sex-changing fish know when they should or shouldn’t change sex?
Many fish change sex during adulthood due to changes in their social environment. Typically, the absence of a dominant male triggers sex change in the dominant female. How male absence initiates such a striking transformation is as mysterious as it is extraordinary. Social position is clearly important, but the behavioural and other cues a female employs to determine her position in the hierarchy and how that influences her decision to change sex or defer to others remain unknown. We hypothesise that cellular and molecular features delineate high-ranked females predisposed to change sex from their peers and are involved in priming or influencing the molecular and neural systems that go on to initiate sex change. Here, using an elegant and powerful combination of behavioural assays, social induction of sex-change, and leading-edge approaches in neuroscience and genomics, we will obtain unprecedented insight into the determinants of female social hierarchies. We will determine those traits and cues that are used to establish these hierarchies, reveal how an individual’s position in its social hierarchy impacts upon its capacity to change sex and decipher the behavioural cues and molecular events that precede and encompass the initiation of socially regulated sex change.
Professor Mark Hampton, Pathology and Biomedical Science, University of Otago Christchurch
Recovery of red blood cells from oxidative stress: a window on human ageing
Ageing is a major risk factor for many human diseases, but there is limited information on the underlying biochemical and molecular processes involved. A common feature of metabolism is the everyday transfer of electrons to oxygen, generating reactive oxygen species that damage our cells. Oxidative damage accumulates in aged tissues, but it is unclear if this damage is a cause or a consequence of ageing. While studying blood samples from healthy middle-aged people, Professor Hampton and his team observed an association between the rate at which the red blood cells from these people recovered from an oxidative challenge and how fast the donors were ageing. Professor Hampton and his team will work with blood donors of different ages to understand the genetic and environmental factors that influence how quickly proteins called peroxiredoxins inside red blood cells return to their normal state after exposure to oxidative stress. Red blood cells may be valuable predictors of how fast other cells in the body are ageing and provide a window into what is happening at a molecular level. This study is one of the few that is taking a close look at fundamental processes associated with human ageing prior to the emergence of age-related disease.
Dr Courtney Ennis, Chemistry
Laboratory exploration of co-crystal minerals for planetary chemistry: Assisting NASA Dragonfly's search for the origins-of-life on Titan
The Dragonfly spacecraft to Saturn's largest moon Titan will embark in 2027 with a primary objective to locate chemical species central to astrobiology and the origin-of-life. To assist in this mission, our laboratory research will explore geochemical pathways toward complex, nitrogen-bearing molecules within Titan's atmosphere and icy terrain. Co-crystals are composite molecular minerals thought particularly conducive to efficient condensed-phase chemistry. Through preliminary calculations, our team have identified a new class of Titan relevant co-crystals possessing an inherently mixed composition of cyanide and hydrocarbon compounds. Forming aerosols within the lower stratosphere, the exposure of co-crystals to Titan's harsh radiation environment is expected to generate a suite of biological building-blocks that are deposited on the surface. To investigate this hypothesis, crystallographic studies of novel co-crystal minerals will be performed at x-ray and neutron facilities. In simulating Titan geochemistry, the subsequent photolysis of co-crystal surfaces will reveal information on the formation of biologically important compounds from cyanide ices. An ensuing detection of nitrogenous heterocycle molecules, such as indole and quinoline biological scaffolds, will provide new principal targets for Dragonfly exploration. If discovered on such outer Solar System surfaces, our laboratory confirmed pathways for these essential biological precursors will have profound implications toward astrobiology.
Dr Christoph Goebl, Pathology and Biomedical Science, University of Otago Christchurch
A novel amyloid formation mechanism ignited by oxidation
Protein amyloids are polymeric, fibrillar structures that are associated with cellular stress or disease. It is unclear how amyloid formation is triggered in biological systems. We recently discovered that oxidation of the tumour suppressor protein p16 sparks its amyloid formation. p16 inhibits cell division and is amongst the most mutated proteins in cancers. We propose that formation of p16 amyloids is an alternate mechanism for loss of function. In this project, we will define the novel mechanism of p16 amyloid formation. We will delineate the critical oxidation event, investigate the polymerisation process and determine the impact of common cancer mutants of p16. We will assess the breadth of this novel amyloid formation mechanism across all members of the p16-like tumour suppressor family. Our team consists of emerging scientists with international experience and world-leading experts in the field of amyloid research. This study will generate new knowledge of a unique amyloid formation mechanism that, for the first time, combines the fields of amyloid biology, oxidative stress and cancer, thereby addressing a crucial knowledge gap in tumour biology. This knowledge will establish the basis for future efforts to translate our findings into improved cancer diagnostics and treatment regimes.
Dr Euan Rodger, Pathology, Dunedin School of Medicine
Taking the driver's seat: suppressing tumour metastasis by eliminating epigenetic drivers
The main cause of cancer-related death is metastasis – the aggressive spread of tumours to distant organs. Despite this profound impact, causal molecular events for metastasis are yet to be identified. Although genetic mutation does not appear to be a causative factor, our work indicates that epigenetic changes such as DNA methylation are critical. However, until recently it has not been possible to directly demonstrate that specific DNA methylation changes alter metastatic potential. To address this long-standing question, here we use a novel approach to unequivocally show that eliminating specific driver methylation changes will suppress metastasis. We will generate high-throughput DNA methylation and expression landscapes of matched primary and metastatic tumours to identify putative epigenetic drivers. We will then use state-of-the-art epigenetic tools to exclusively 'edit' the epigenetic drivers in cancer cells. Implanting these edited cells into a preclinical model will provide direct evidence for the role of epigenetic changes in altering metastatic capability. We aim to demonstrate for the first time that DNA methylation changes act as a driver of metastasis. This will open new avenues for understanding metastasis biology, lead to better outcome prediction, and identify new targets to treat aggressive tumours in the future.
Associate Professor Tobias Langlotz, Information Science
Egocentric Vision Augmentation - Coherent visual integration for AR through real-time view modelling
Augmented Reality (AR) glasses are predicted to become omnipresent in our everyday lives. Unlike printed instructions or traditional displays, AR shows information as a visual overlay integrated into our environment. Think about surgeons using AR glasses to view scans overlaid onto the patient during surgery or instructions helping users assemble their furniture. Unfortunately, the expected advantages in usability and effectiveness of AR interfaces are diminished by the imprecise visual integration leading to two distinguishable “layers”, our physical environment and the digital overlay. But how can we visually integrate information into the user’s view if we do not know how the world looks to the user? This project will be the first to address this fundamental issue, which we termed ego-centric vision. Inspired by light fields and image-based rendering, we will in a first step interactively compute the ego-centric vision of the user. In a second step, we investigate a seamless visual integration utilising real-time ego-centric vision to render a coherent visual overlay, a crucial functionality for the future success of AR. This project will offer substantial contributions to the academic literature by addressing fundamental questions in AR glasses technology and ego-centric vision with both having significance to other disciplines.
Associate Professor Stephanie Hughes, Biochemistry, School of Biomedical Sciences
The missing link: LncRNA regulation of lysosome function in brain disease
A healthy brain requires a functional waste recycling system. In human neurons, lysosomes are ultimately responsible for waste recycling. Additionally, lysosomes also transport RNA molecules and regulate neuron function as secondary responsibilities in neurons. Defects in lysosomes lead to the accumulation of cellular waste in the brain cells, ultimately contributing to the development of human brain diseases. In our group, using human neurons grown in a dish, we have replicated a human brain disease, which shows defective lysosome function. Intriguingly, the defective lysosomes were also associated with changes in a group of RNA molecules, called lncRNAs (NeuroLncs). LncRNAs are known for a multitude of regulatory functions. However, whether lncRNAs can regulate lysosome function, remains unexplored. We hypothesise that lncRNAs control lysosome function. To test our hypothesis, we will alter the expression of the identified NeuroLncs in our human neurons and analyse lysosomal and neuronal function. The outcomes from our proposed study will unveil a new chapter of cellular regulatory mechanisms exploring the missing link between lncRNAs and lysosomes. This work will open a brand-new field of neurobiology with the potential for the development of RNA therapeutics for brain diseases in the future.
Dr Sharon Ladyman, Anatomy, School of Biomedical Sciences
Neurons to keep mums cool
A recently identified population of neurons in the preoptic area of the brain can profoundly reduce body temperature, but their role in a physiological context is unknown. We discovered that these neurons express receptors for the pregnancy hormone, prolactin. This suggests that they may be important in regulating maternal body temperature during pregnancy, when maintaining appropriate temperature is a critical challenge, due to increased metabolic heat generated by fetal growth (“cooling for two”!). We aim to investigate whether prolactin acts in these thermoregulatory neurons during pregnancy to sensitize their response to elevations in body temperature, resulting in more rapid and powerful activation of physiological and behavioural responses to decrease body temperature. Using transgenic mouse lines in which prolactin receptors are deleted from these thermoregulating neurons, we will investigate the consequences for the pregnancy and subsequent lactation if these hormone-induced adaptations in thermoregulation do not occur. This work will provide novel insight into plasticity of thermoregulation and demonstrate a key physiological function of these recently identified thermoregulating neurons. This may have important implications, for example for sustaining healthy pregnancy and good levels of milk production in warmer climates.
Dr Mei Peng, Food Science
How do sensory shifts shape our diet? - Testing the neural mechanisms underpinning nutrient selection
Is there an underlying sensory neural mechanism ‘secretly’ guiding our food choices? It remains unclear how and why individuals choose such different energy sources. Tantalisingly, recent data suggest that individual metabolic needs can substantially influence dietary choices, implying the existence of an autonomic system driving nutrient intake. While all individuals can experience metabolic shifts across their lifespans, pregnancy provides a unique window into major metabolic reprogramming. In this project, we will use pregnancy as a natural model to understand how the human brain adjusts to changing metabolic needs through food choices. Untangling the sensory neural mechanisms guiding individual food choices will enable effective interventions to manage obesity and related disease.
Dr Michael Garratt, Anatomy, School of Biomedical Sciences
Beyond sperm transport: how seminal fluid shapes the female life course
Reproduction has long-term consequences for the mother, influencing her subsequent fertility and rate of ageing. The biological causes of these changes are largely unknown. We have made the startling discovery that the act of mating by itself elicits major changes to a female animal’s life-course, increasing growth and fertility but shortening lifespan. This occurs even without sperm in the ejaculate, suggesting that factors in seminal fluid other than sperm cause these remarkable effects. This project will directly manipulate the transfer of seminal fluid during mating in mice, to establish whether this is the causal stimulus that influences female growth, fertility and ageing. We will also test whether life-course responses to mating vary with the degree of immune reaction elicited by seminal fluid exposure. Seminal fluid transferred at mating generates an immune response in females that helps with gestational development. We hypothesize that these immune responses persist across life and help females reproduce with previously experienced males in the future, but also contribute to the reduced lifespan caused by mating. The proposed research could reveal far-reaching effects of seminal fluid exposure beyond sperm transport, providing new insights that could help manage and improve livestock productivity and human health.
Associate Professor Zach Weber, Philosophy
Paraconsistent Computability Theory
What is an algorithm to do if a given parameter—e.g., 'flight cancelled'—has both values ‘YES’ and ‘NO’ simultaneously? Experts have believed since the 1930s that there are fundamental limitations to how an algorithm (any algorithm) can cope with inconsistent information. Until now, the answer to ‘Can an algorithm successfully compute beyond an inconsistency?’ has been held to be negative—the best that can be achieved is some form of graceful failure. But this question has been reopened, due to recent advances in philosophical logic. Paraconsistent logic makes it possible to compute beyond inconsistency. By using new formal tools this project will pioneer a new field, building paraconsistent algorithms with the potential to surpass previous limits.
Dr Jeff Erickson, Physiology, School of Biomedical Sciences
Targeting CaMKII to tune cardiac structure and restore function in the diabetic heart
Cardiovascular disease is the top cause of death in diabetic patients due to reduced function and increased stress on the heart. Despite this, there is no diabetes-specific cardiac treatment to improve cardiac function, and the underlying cause of reduced contractile function in the diabetic heart is not well understood. Recent work by our lab and others has identified the cardiac kinase CaMKII as a key mediator of cardiac pathology during diabetes. These observations suggest that CaMKII may be a novel therapeutic target to prevent structural remodeling and preserve cardiac function in the diabetic heart. In this application, we propose to examine changes to calcium channel organization, myofilament calcium sensitivity, and tissue-wide structural alterations that contribute to reduced function during diabetes. We propose to target these structural changes using genetic ablation of CaMKII in a model of type 2 diabetes to reverse loss of contractile function, a novel approach for the prevention of diabetic cardiomyopathy. This project will be, to the best of our knowledge, the first ever to examine key structural features of the diabetic myocardium to determine a root cause for reduced contractile function, as well as the first to attempt to prevent pathological remodeling by ablation of CaMKII.
Dr Nathan Kenny, Biochemistry, School of Biomedical Sciences
Investigating the roots of resilience to climate change in kuku at single cell resolution
Molluscs such as kuku (Perna canaliculus) are vital to our ecosystems, and taonga of cultural and economic importance. Climate changes, including temperature extremes and ocean acidification, threaten this species, but while some kuku show resilience to these problems, others remain vulnerable. The source of resilience is unknown, but differences in early development are strongly implicated. Using cutting-edge approaches, led by single-cell RNA sequencing, we will pinpoint the key differences exhibited by resilient kuku. These could be resources provided by the mother, or genes activated in initial stages of development. We will trace these through the normal development of kuku and discern the downstream impact of these changes on later maturation. This will provide an unparalleled window into the growth of this species, at cellular-level detail. The data gained in this work will be a revolutionary resource for understanding normal bivalve development. Clues as to the source of resilience to the pernicious effects of climate change will also greatly assist conservation and aquaculture efforts in both kuku and other mollusc species. This work will therefore provide both fundamental knowledge and applied outcomes and help us preserve this fascinating and treasured species.
Dr Annie Sohler, Anatomy, School of Biomedical Sciences
Embodied Colonialism: Bio histories of 19th-century Pākehā and Chinese Migrants to New Zealand
"Embodied Colonialism" will explore how migration to Aotearoa impacted the health of 19th century Pākehā and Chinese peoples. The mid-19th-century saw waves of immigration to New Zealand, first from Europe and then from Southern China following the discovery of gold in Otago. The first generation of Cantonese and Pākehā experienced significant environmental and social changes associated with relocation to the Deep South. Recent exhumations of early settlers and gold miners from Otago cemeteries have provided a unique opportunity to learn who these people were. Stresses associated with environmental and social change leave their signatures and time stamp in human remains and recovery of this information provides a powerful lens into past lives. By examining microscopic markers of stress and disease in tissues that form during childhood and those that form in adulthood, a longitudinal portrait of a person's health over time can be reconstructed. Bioarchaeological techniques, including microscopic analysis of teeth and retrieval of pathogen DNA in the skeletons will be integrated with archival research to reconstruct the biological history of each migrant, from stresses suffered during childhood in their “home” country to their death in New Zealand, revealing the embodied effects of migration and environmental adaptation.
Dr Gert-Jan Jeunen, Anatomy, School of Biomedical Sciences
Molecular time-capsules of oceans past – reconstructing Antarctica’s marine ecosystems using historical environmental DNA from marine invertebrate collections
Our oceans are under siege from increasing anthropogenic pressures. Mitigation and restoration of degraded marine systems is of top economic and ecological importance. However, successful remediation requires detailed knowledge of how these ecosystems have altered over time. Currently, the extent and speed of ecological change in the marine domain has rarely been quantified, because long-term ecological records are scarce and accurate historical data difficult and expensive to obtain. Recently, we showed that marine filter-feeding organisms accumulate eDNA, which can be used to reconstruct the biodiversity of marine environments. Vast numbers of filter feeders have been gathered over centuries and are stored in scientific collections. These archived samples provide unique ecosystem time-capsules through which we can reconstruct ecosystem states using new historical eDNA approaches. Antarctica's Ross Sea, a region of significant national and international research focus, is particularly well represented in collections. Here, by linking historical with contemporary eDNA surveys at matching sites in the Ross Sea, we will investigate how regional biodiversity has altered over 70 years. Using these data, alongside information on industrialisation, bio-invasion and climatic change, we will gain new insights into how the Ross Sea ecosystem has altered during a period of extraordinary anthropogenic and climatic changes.
Dr Joon Kim, Physiology, School of Biomedical Sciences
How does stress cause anxiety?
Stress is one of the most commonly described contributing factors in the development of anxiety disorders; and yet, it is unknown how stress neural circuits in the brain control anxiety. The stress response is controlled by a population of neurons in the brain called corticotropin-releasing hormone (CRH) neurons. My preliminary findings show that acute elevations in CRH neural activity are associated with a switch from low anxiety to high anxiety behaviours. The aim of this research is to understand how CRH neurons mediate this behavioural switch. It is hypothesised that CRH neurons gate anxiety states in an activity-dependent manner; whereby high CRH neuron activity causes anxiety and low CRH neuron activity reduces anxiety. To test this, I will use a combination of optical techniques that can simultaneously manipulate and record the activity of CRH neurons in behaving mice. Furthermore, using a novel dual-recombinase approach, this research will interrogate the output circuitry of CRH neurons to understand how the communication between discrete neural populations in the brain causes changes in anxiety states. This research will provide the first evidence of how CRH neural circuits affect anxiety and begin the foundations to understand how stress affects the mind.
Dr Chun Shen Lim, Biochemistry, Physiology, School of Biomedical Sciences
Deciphering translation of the ‘untranslated’ regions of messenger RNAs
The regulation of gene expression is critical for the normal cellular function and the development of multicellular eukaryotes. We have recently found an undescribed mechanism that regulates gene expression, through splicing and translation that occur at the 5′ untranslated regions of messenger RNAs. This links splicing and translation, key sequential cellular processes that occur in two separate cellular compartments. We estimate that ~30% of messenger RNAs are regulated by this new mechanism. We propose that such messenger RNAs can be translated to build two or more different peptides or proteins, due to an alternative type of translation on the 5′ ‘untranslated’ regions. The goal of this research is to understand how this new regulatory mechanism works. I will lead an international team to study this mechanism in human, insect, and plant systems using a combination of new computational and laboratory techniques. We predict that this mechanism is conserved across diverse species and anticipate that the study will open up new avenues across research disciplines such as in biomedicine and agriculture.
Dr Drew Oliphant, Biochemistry, Physiology, School of Biomedical Sciences
Making heads or tails of bees: understanding the evolution of the first stages of embryogenesis
We aim to identify genes which determine head (anterior) from tail (posterior) early in embryo development for the honeybee, Apis mellifera, and bumblebee, Bombus terrestris. Organising the anterio-posterior (A-P) axis underpins all animal development, but surprisingly for a process so fundamental to normal development, it appears to evolve rapidly among insects. This provides the opportunity to study how genes evolve novel functions as A-P axis determinants. We have RNA-sequence datasets from which we have identified genes with potential roles in A-P axis organisation for honeybees and bumble bees. By supressing gene expression, we aim to reveal gene function in embryo development and discover any changes in A-P axis organisation between these closely related bees. Further, by investigating in other hymenopteran species the genes that organise the A-P axis for honeybees and bumble bees, we aim to explore when these genes evolved these roles.