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2019 PhD Projects

New PhD Projects for 2019

Applicants are encouraged to contact potential supervisors to discuss project details and reach out to a university to discuss entry requirements. All projects and applicants are subject to approval by the Melbourne Children's Graduate Research Committee. 

See our PhD page for information about PhD program applications and scholarships.

Projects by Theme:

Cell Biology

Clinical Sciences

Genetics

Infection and Immunity

Population Health

Data Science

Project Descriptions:

Human Testis Organoids From Stem Cells - A Novel Model For Reproductive Disorders

Often the first question asked when a child is born is "is it a boy or a girl". Unfortunately, a definitive answer cannot be given to the parents of a child born with severe ambiguous genitalia. These cases occur with a frequency of 1 in 4500 births and are part of a large spectrum of disorders known as Disorders/Differences of Sex Development (DSD), which are caused by mutations in the genes that regulate how the testis or ovaries develop and function. Yet, less than 50% of patients with DSD currently receive a clinical genetic diagnosis. This is due to a very poor understanding of the genes that can cause DSDs. We use genomic technologies such as Whole Exome Sequencing to find novel candidate genes that may cause DSDs. We currently test the importance of these gene in the developing gonads (testis or ovaries) using animal models such as mice. However, mouse gonadal development is not always a good model for human gonadal development and disease. Consequently, we are developing stem cell technology to grow human testicular cells in a dish. This project involves optimising the differentiation of human testicular cells from pluripotent stem cells, and growing these to organoid formation. These organoids will then be used to test the importance of new candidate pathogenic gene variants found in DSD patients. This project will be conducted in collaboration with Professor Melissa Little, who has successfully grown human kidney organoids, and used these to model kidney disease. It will suit someone who has an interest in working with cutting edge stem cell technology and genomic analyses to study disease. 

 
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Identification Of New Genes That Cause Disorders/Differences Of Sex Development 

Often the first question asked when a child is born is "is it a boy or a girl". Unfortunately, a definitive answer cannot be given to the parents of a child born with severe ambiguous genitalia. These cases occur with a frequency of 1 in 4500 births and are part of a large spectrum of disorders known as Disorders/Differences of Sex Development (DSD), which are caused by mutations in the genes that regulate how the testis or ovaries develop and function. Yet, less than 50% of patients with DSD currently receive a clinical genetic diagnosis, due to a poor understanding of the genes that can cause DSDs. This project will use genomic technologies such as Whole Exome Sequencing and targeted microarrays to find novel candidate genes that may cause DSDs. In this project, you will analyse DSD patient sequencing data for potential pathogenic gene variants in an effort to identify novel candidate genes. These genes will then be validated using lab technologies such as immunofluorescence staining on embryonic gonads and qRT-PCR. This work will uncover novel genes that contribute to DSD in humans and improve diagnosis rates for patients with these difficult disorders.

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Unravelling The Genetic Cause Of Premature Ovarian Insufficiency

Premature Ovarian Insufficiency (POI), affecting as many as 1 in 100 women, is a form of female infertility characterised by lack of menstruation and menopausal hormone levels before the age of 40. In some cases, young girls fail to get periods altogether and learn they have this menopause-like condition in early adolescence. POI not only interferes with a woman's reproductive potential, but is also associated with an increased risk of osteoporosis, mental health problems, cardiovascular disease, and earlier death. 

Ample evidence indicates the genetic basis of POI, however, its genetic cause is complex with implicated genes having roles in various cellular processes. The majority of cases remain unexplained, limiting appropriate treatment and management of affected individuals. 

We have DNA from the largest described cohort of women with POI (N>100), and we are using the latest genomic technologies to identify novel causes of the condition. In this project, you will mine sequencing data for pathogenic gene variants and perform experimental validation to prove causality. This will involve techniques such as western blotting, gene expression assays, qRT-PCR and immunofluorescence staining in control and patient cell lines. This project has already revealed some exciting new candidate genes involved in POI. 

Your project will contribute to better treatment and counselling of affected individuals, as well as enabling the identification of family members before symptoms arise. This can allow early intervention such as cryopreservation of eggs and hormone-replacement therapy to minimise co-morbidities. Discovering new "disease genes" improves understanding of the process of ovarian biology, which can then enable the development of therapeutics which are largely lacking for this condition. 
 

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How Do Monocytes Remember? Characterisation Of The Early Life Exposures That Induce Innate Immune Memory

We all know that the adaptive immune system develops memory following specific antigen exposure, but is the same true for the innate immune system? An emerging field of research tells us exactly this, with epigenetic remodelling as the underlying mechanism. Innate immune cells, such as monocytes and macrophages, form this non-specific memory in response to a variety of exogenous signals. Exposure-induced epigenetic remodelling governs their future response to a range of pathogens. This process can be modelled in vitro, using both yeast and bacterial antigens and metabolites (Novakovic et al. Cell 2016), metabolites (Bekkering et al. Cell 2018), vaccines (Arts at el. Cell Host Microbe 2018) and a range of other stimuli.

During pregnancy, both maternal and foetal monocytes show attenuated pro-inflammatory responses correlated with pregnancy-associated hormones. Additionally, foetal monocytes are exposed to a range of environmental factors. We hypothesise that monocytes remodel their chromatin in response to early life environments, which explains their altered function during pregnancy. To test this hypothesis, we will isolate pure monocytes from human blood, and treat them with various stimuli in vitro. After treatment we will measure cytokine release, RNA expression and epigenetic (histone modification) changes. This project is appropriate for students with an interest in molecular biology and immunology and will utilise monocyte isolation and culture, ELISA, chromatin immune-precipitation (ChIP), DNA and RNA extraction and real-time PCR.

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Early Life Molecular Pathways Underpinning Later Health And Disease

The world is experiencing an alarming rise in the incidence of cardiovascular disease, obesity and poor metabolic health (collectively referred to as cardiometabolic disease). Mounting evidence suggests that the in utero and early postnatal period plays a critical role in programming these complex adult phenotypes. Genetic and environmental factors contribute to complex disease risk and influence both epigenetic and metabolomic profiles, which have emerged as prime candidate mediators for the early life programming of later cardiometabolic health. Epigenetic and metabolomic variants therefore have great potential as biomarkers for identification of individuals most at risk for targeted intervention, and for monitoring disease progression. The overall aims of this project are to examine the association between, genetic, environmental, epigenetic and metabolic variants, using longitudinal measures of adiposity and cardiovascular health in the unique Barwon Infant study (BIS) of 1000 mothers and their children (www.barwoninfantstudy.org.au/). BIS has a wealth of environmental measures and longitudinally sampled biospecimens with genome-wide genetic data already collected, enabling an unprecedented investigation of the role of genes, environment and epigenetic/metabolomic biomarkers in conferring early life risk of cardiometabolic health in humans.

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Developing New Therapies For Childhood Heart Disease Using Stem Cell Technology

An opportunity exists for a highly motivated post-graduate student to join a multidisciplinary research group working on the molecular mechanisms underlying congenital heart disease. The student will have the opportunity to work on a multi-disciplinary, collaborative project utilising genetically engineered induced pluripotent stem cell (iPSC) models of congenital heart disease. The student will receive training and develop expertise in a number of key areas at the forefront of biomedical research including genome editing, flow cytometry, molecular biology techniques, bioinformatics and confocal microscopy. A particular focus of this project is to develop disease models and to use these as a platform to develop high-throughput screens for novel compounds targeting the biochemical pathways underlying myocardial disease or to develop cellular therapies for congenital heart disease. The PhD candidate will have a unique opportunity to work as part of a cross-disciplinary team including stem scientists, clinicians and bioengineers interested in tackling childhood heart disease and developing new therapies. Projects can be designed to align with the PhD student's areas of interest and previous training.

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Modelling Human Cartilage And Bone Disease Using Pluripotent Stem Cells

    Human skeletal development and proper bone, cartilage and joints function are determined by complex signaling network interactions. Genetic and acquired disorders affecting these tissues are common. Our research is aimed at understanding the molecular basis of these disorders and identifying new therapeutic targets. For this we are using human induced pluripotent stem cells to produce world-first in vitro cartilage and bone "disease-in-dish" models.

    Human iPSC lines for various bone and cartilage gene mutations are made from patient fibroblasts and the mutations are corrected using CRISPR/Cas9 genome editing to generate control cell lines with an identical genetic background. These iPSCs will be differentiated into cartilage and bone in cell culture and the downstream consequences of the mutations monitored by transcriptomics (RNASeq) and proteomics, fluorescent activated cell sorting, confocal microcopy, histology and cell biology techniques such as protein immunoblotting. Disease networks will be identified by gene-protein network analysis using bioinformatics tools. These analyses will point to new therapeutic targets which will be tested using targeted drug libraries in our "disease-in-dish" models.

    PhD candidates will be trained in cutting edge techniques including: genome editing, stem cell manipulation, transcriptomics, proteomics, bioinformatics and other cell biology techniques. Our research is funded by several ongoing NHMRC and international grants.

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    Evaluating Health Outcomes Of Transgender Children And Adolescents

    Referrals of young transgender individuals to clinical services are rising exponentially across the western world. Consistent with this, recent population-based estimates suggest that the prevalence of young people identifying as transgender is 1%, which is much higher than previously thought.

    Providing optimal clinical care for transgender young people is critical. A recent community-based survey of 859 Australian trans youth found a significant proportion had been diagnosed with depression (74.6%) and anxiety (72.2%), with 79.7% of respondents reported having self-harmed and 48.1% having attempted suicide. Many of these young people had never accessed gender-affirming health care, and there is increasing evidence that providing supportive clinical care to transgender youth significantly improves mental health and wellbeing.

    The Royal Children's Hospital Gender Service (RCHGS) provides care to transgender children and adolescents, and is one of the largest multidisciplinary clinics of its kind in the world. While our team recently released the first ever clinical guidelines specific for transgender children and adolescents - as highlighted by a recent editorial in The Lancet - there is still a lack of good research data to inform clinical practice in this nascent field.

    To address this gap in knowledge, the RCHGS commenced a longitudinal cohort study known as Trans20 at the start of 2017. Trans20 aims to evaluate the clinical outcomes of individuals receiving care through the service, and is currently on track to enrol >600 patients into the study during 2017-8. Data is collected annually across multiple domains, including gender identity, mental health, physical health, quality of life and family functioning. This rich dataset offers a tremendous opportunity for interested PhD students to address important questions in the field of transgender health. In particular, candidates with an interest in transgender health, and a background in psychology, paediatrics, psychiatry, or endocrinology are encouraged to apply. 

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    Developing Objective Measures To Improve Outcomes In ADHD

    We are seeking to recruit a recruit a high quality graduate (medicine, psychology/neurosciences) to undertake a clinical study in children aged 5 - 14 years with a diagnosis of ADHD. This study will be run jointly by the Murdoch Children's Research Institute and the Complex Human Data Hub, School of Psychological Sciences, University of Melbourne. The proposal is to recruit a sample of children with well characterized attention deficit/hyperactivity disorder at the time of their diagnosis. Each participant will be thoroughly assessed at baseline using state of the art clinical and cognitive assessments. Sample collection for bio-banking will also be completed to link with future discovery research. Each participant will then wear an energy-efficient multi-sensor wearable device (such as a fitbit) continuously for several weeks to gather real time data on activity levels, sleep, pulse-rate. These data will be used to define baseline performance across the day. All participants will then be engaged in treatment as usual from their regular clinical service provider. We will continue to measure the continuous data from the wearable device and collect regular treatment data and clinical outcome measures. The aim is to develop novel approaches to measuring outcome through continuous objective measures that allow the optimization of treatment across the day. To achieve this objective we will work with colleagues at the Complex Human /Data Hub who will provide support and guidance on data management and analysis. Analysis will involve a broad range of traditional and modern approaches to analysis such as using a range of approaches such as Baysian and machine learning approaches to determine the most efficient and meaningful way of objectively measure the progression of symptoms across the day to facilitate treatment optimization.

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    Deepening Our Understanding Of Severe Irritability In Children

     We are seeking to recruit a recruit a high quality graduate (medicine/psychology/neurosciences) to undertake a clinical study in children aged 5 - 14 years with severe irritability. This study will be run jointly by the MCRI and the Complex Human Data Hub, School of Psychological Sciences, University of Melbourne. The proposal is to recruit a sample of children with severe irritability referred to child and adolescent mental health services. Our aim is to understand the mechanisms underpinning individual differences in children and adolescents with severe irritability. Developing a better understanding of the mechanisms underpinning severe irritability will improve early detection and intervention with the aim of reducing impairment and limiting progression to latter difficulties. The proposal is to establish a well-characterized cohort of children with severe irritability. Each participant will be assessed at baseline using state of the art clinical assessments to assess: current and past mental and physical health; antenatal, developmental and family histories; neurocognitive assessments using well validated clinical and neuroscience based measures. We will also investigate the use of energy-efficient multi-sensor wearable devices, other mobile technologies and the Internet of Things, to detect and measure novel markers of disorder and functioning in real time and with minimal demand or interference with day to day activity. In collaboration with colleagues at the Complex Human Data Hub these date will be integrated across the different levels of analysis traditional and modern approaches to analysis such as using a combination traditional and modern approaches such as Baysian and machine learning in order to identify heterogeneity within this group of children and adolescents, build explanatory and predictive models that can aid clinicians in their assessment, diagnosis and treatment of severe irritability and better understand the course and developmental trajectories for irritable children.

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    Understanding The Development Of Cognition And Academic Performance

     We are seeking to recruit a high quality graduate (psychology/neurosciences) to contribute a population based study in children and adolescents aged 5 - 18 years. This PhD project will focus on developing specific questions and hypotheses relating to the developmental associations between cognition and academic and psychopathology through childhood and adolescence, collecting the first wave of data for the study and analyzing this cross sectional data with a specific focus on the questions relating to cognition and psychopathology. The overarching aim of the study is to recruit a sample of children and adolescents from schools within Melbourne. For each child we will collect information about intelligence, psychopathology, academic achievement, functioning and quality of life as well as bio-samples that can be bio-banked for future analyses. Each participant will also complete a series of cognitive tasks from the well-known CANTAB battery. Tasks will assess the various aspects of cognition and include tasks with both high and low executive demands. These tasks have been chosen because they were developed from a neuroscience rather than clinical perspective and are all associated with specific neural substrates. All subjects will be tested on at least two occasions. Through these data we will be able to better understand memory development and the development of behaviour brain relationships across childhood and adolescence as well and define the normative relationships between memory, psychopathology, functioning and quality of life through these developmental stages. Together these data will provide important insights into the development of behaviour brain relationships and facilitate the development of much needed 'growth charts' for memory development that can be used as a yardstick for future studies exploring abnormal development and neurodevelopmental disorders.

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    Are Psychological Factors Associated With Participation Outcomes In Children With Cerebral Palsy?

    Cerebral palsy is one of the most common neurodevelopmental conditions in childhood, affecting 2-3/1000 children. While motor impairment is the hallmark feature of this condition, children with cerebral palsy also often experience significant cognitive, communication, and behavioural difficulties that further reduce participation in school, play and socialisation. Demographic and illness-related variables only account for a small proportion of the variance in participation outcomes. This study will evaluate the association between participation outcomes and psychological (anxiety, depression), family factors (family functioning, parental distress), and personal factors (resilience) in children with cerebral palsy. It is hypothesized that resilience and psychological factors will make an independent contribution to participation outcomes in children with cerebral palsy. This study forms part of a larger project to develop a new mental health model of care for children attending the Victorian Paediatric Rehabilitation Service. Children aged 0-18 years with a diagnosis of cerebral palsy attending the Victorian Paediatric Rehabilitation Service and/or their parents will complete a series of questionnaires at the time of admission and again 6 months later. This project offers an opportunity to work with an experienced interdisciplinary team of researchers and clinicians with expertise in child disability and mental health outcomes.

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    Influence Of Pubertal Hormones On Brain Development

    Puberty is a time of rapid change within the brain. Whilst the biological basis for this change remains uncertain, changes in sex hormones, such as oestrogen and testosterone likely play an important role. However, puberty also coincides with other major changes, including the onset of more complex social interactions and educational experiences, which might also influence brain development. Separating out the role of environmental influences and hormonal effects on brain development has traditionally been difficult. 

    The Royal Children's Hospital Gender Service provides care to transgender children and adolescents, and is one of the largest multidisciplinary clinics of its kind in the world. Many of our patients are treated with medication to block the production of pubertal hormones in order to prevent their bodies developing in a way that is incongruent with their inner gender identity. This use of puberty blocking medication typically occurs for several years, and provides an opportunity to learn how the teenage brain develops in the absence of sex hormones.

    This PhD project will therefore seek to address specific questions and hypotheses relating to the role of sex hormones on cognition during adolescence, and will at the same time provide important insights on the cognitive effects of using puberty blocker medication in young transgender individuals. The project will involve collection of the first and second wave of data from patients receiving puberty blocking medication and a matched control sample from local schools. We will use cognitive tasks from the well-known CANTAB battery, which have been chosen for their strong associations with specific neural substrates and ability to thus provide a window into brain development. We will also include a range of tasks that assess social aspects of cognitive development. High quality graduates with a background in medicine/psychology/neuroscience are encouraged to apply.

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    Cord Blood Stem Cell Adjunct Therapy For Paediatric Heart Failure

    A high risk of heart failure complications and death is faced by children with severe congenital heart disease such as hypoplastic left heart syndrome (HLHS), and by children with dilated cardiomyopathy or severe myocarditis requiring ventricular assist device implantation and support. HLHS requires extensive complex surgical reorganisation of the neonatal heart, however metabolic supply-demand insufficiencies limit postoperative recovery at a time when neonatal myocardial growth and increased myocardial performance is required. For cardiomyopathy patients, workload-dependent energy demand, pressure and volume load in excess of capacity drives progressive worsening of myocardial dysfunction, cardiac remodelling and heart failure. Their survival requires mechanical assist device implantation to permit ventricular unloading and increased cardiac output. In both patient cohorts cardiopulmonary bypass surgery is a first step in initiating respective treatments. Despite advances in surgical intervention to augment survival of HLHS patients and technological advances in ventricular assist devices to support cardiomyopathy patients, further advances are required to target myocardial remodelling directly at a cellular level. Our current work examines how cord blood stem cells influence adaptive processes involved in muscle growth and metabolism, inflammation and fibrosis and their therapeutic potential in the cardiac surgical setting by promoting increased myocardial mass and function. Our key goal is to translate protective heart muscle fortification strategies to prevent death from heart failure. Recently, we demonstrated a new method of delivering cord blood stem cells to the neonatal myocardium using an experimental animal model of neonatal cardiopulmonary bypass surgery. Our multidisciplinary team has commenced a clinical safety trial in the cardiac surgical setting. Project goals involve testing cellular and mitochondrial metabolism, stem cell exosome signalling, cell-cell interactions in vitro and in surgical models, in addition to clinical trial work. More than one project is available for Biomedical Science or Medical graduates according to student background and interests.

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    Applying New Genomic Technologies To Understand The Genetic Basis Of Autism Spectrum Disorder

    Autism Spectrum Disorder (ASD) is a complex and highly heritable neurodevelopmental disorder defined by deficits in social communication and repetitive behaviours with restricted interests. Over 300,000 Australians have ASD and the annual national economic cost is ~$9.7 billion. ASD typically display complex inheritance but the genetic basis underpinning the disease remains largely unexplained. This project aims to understand the genetic basis of ASD by performing genetic studies in large families with 2 or more affected children. Novel genes will be characterised to understand pathogenic mechanisms underlying disease utilising advanced molecular and cell biology techniques. Subsequent studies will utilise newly developed and unique iPSC models to perform preclinical studies to characterise the disease process and identify potential therapeutic targets. This project is multidisciplinary and involves close collaborations with clinical researchers and bioinformaticians. The outcomes will enable understanding of the molecular basis of ASD and identify potential therapeutic targets for clinical management.

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    Using Cerebral Organoids For The Study Of Tuberous Sclerosis Complex

    Tuberous sclerosis (TSC) is a multi-system disorder leading to benign tumours in several organs including the skin, kidney, heart, lung and brain. The most significant clinical sequelae of TSC are neurological, with epileptic seizures being the most common and severe, particularly when they occur in early childhood. The seizures are often resistant to treatment with drugs and arise in abnormal brain regions called tubers. If the seizures are not suppressed or otherwise managed, especially during early childhood, they are often associated with adverse developmental consequences including intellectual disability and autism.

    The ability to model neurological disorders utilising cerebral organoids represents an invaluable tool for both delineating disease processes and investigating the fundamental mechanisms required for normal human brain development. Tubers are three-dimensional structures characterised by markedly disturbed cortical layering and morphologically abnormal cell types. Little is known about the molecular mechanisms leading to tuber development or the mechanism of seizure generation.

    In this project the candidate will developing iPSC-derived cerebral organoid models to investigate the aetiology of tuber formation and resultant epilepsy. They will utilise molecular and cellular techniques including stem cell culturing, differentiation, immunostaining and advanced microscopy to analyse organoid models of TSC. There is considerable scope for collaborative interaction with clinicians and bioinformaticians involved in the program.

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    Understanding Rab39b-Mediated Parkinson's Disease

     The recent advances in our understanding of common and disabling neurodegenerative diseases such as Parkinson and Alzheimer disease has been the result of the identification and analysis of causative mutations in families, where a genetics-based approach can be utilised to identify disease associated genes. We recently identified RAB39B as a novel gene for Parkinson's disease. 
    This project will characterise the gene and investigate pathogenic mechanisms underlying disease utilising molecular and cell biology techniques. Studies will utilise newly developed and unique iPSC and mouse models to perform preclinical studies to characterise the disease process and identify potential therapeutic targets.

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    Identifying The Genetic Causes Of Brain Malformation In Children

    The human cortex is the surface of the brain that enables advanced intellectual function. It forms through a series of overlapping steps involving neuronal proliferation, migration and differentiation. Abnormal formation of the cortex causes a group of disorders known as malformations of cortical development (MCD), which can result in epilepsy, intellectual disability and cerebral palsy. There is considerable evidence that gene mutations cause MCD, but to date few of the genes involved have been identified. This project will utilise modern genomic technologies, including whole exome and genome sequencing and single cell analyses, to identify the genetic basis of MCD. Close collaboration with neurosurgeons and neurologists at the Royal Children's Hospital enables unique access to tissue to investigate relevant disease mechanisms. Newly identified genes will be investigated in model systems, including pluripotent stem cells to determine underlying disease pathogenesis. The successful applicant will work closely with clinicians and bioinformaticians as part of a large multidisciplinary team.

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    Human Stem Cell Models of Mitochondrial Disease

    Mitochondria are our cellular power plants that burn sugars, fats and proteins to generate energy. Each week in Australia a child is born with a mitochondrial disorder. Many of these children die in the first years of life and most suffer from severe disease, particularly affecting their brain and/or heart. Access to these tissues from patients is limited, making it difficult to assess the impact on mitochondrial and other pathways contributing to disease pathology. This project is part of a 5-year NHMRC-funded study to develop and characterize human stem cell models for over 20 genes in which knockout-type mutations cause inherited disorders of mitochondrial energy generation. 
    The overall aims are: 
    1) Assemble a representative panel of cellular models of OXPHOS disease in human Embryonic Stem Cells (hESCs) and human Induced Pluripotent Stem Cells (iPSCs) that can be used to study phenotypic rescue of novel defects, pathogenicity and treatment approaches. 
    2) Characterize pathogenic pathways in the most relevant cell lineages by assessing the impact of OXPHOS defects on the mitochondrial and cellular proteome of cardiomyocytes and neural cells generated from hESCs or iPSCs, as well as the impact on mitochondrial function and cellular physiology. 
    3) Define the impact of targeted therapeutic strategies in these models on the cellular proteome and other markers of cellular homeostasis. 
    The research project will thus involve generation of hESCs with CRISPR/Cas9 mediated gene disruption, or iPCs from mitochondrial disease patient fibroblasts, followed by confirmation of the impact on the targeted gene and pathway. Selected cell lines will then be differentiated to cardiomyocyte and/or neural lineages to enable comparison (with control cells) of the impact of the gene knockout on various aspects of mitochondrial and cellular function. These may include respiration, ATP synthesis, reactive oxygen species, mitochondrial membrane potential, redox balance, cellular stress response and quantitative proteomics. 

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    The Application Of Genomic Testing In Adults With Intellectual Disability

    We hope to recruit a high quality medical graduate/trainee to undertake a clinical and genomic study of adults with intellectual disability. The proposal is to recruit two cohorts of adults with ID, one being adults with ID referred to adult genetics clinics and the other being adults with intellectual disability who have not been referred to genetics, who will be recruited from other clinics that cater to the needs to adults with intellectual disability. All adult patients will undergo clinical assessment and traditional investigations (e.g. microarray, FXS) and will be offered genomic testing via exome sequencing. We will collect and assess data regarding diagnostic yields of clinical assessment, microarray and exome sequencing. We will also study the interest of families in exome sequencing, the acceptability of testing and the clinical utility of genetic testing results. In addition, we will also offer families/guardians the opportunity to receive secondary findings from exome sequencing, and assess interest and uptake of these analyses. A health economic analysis will also be performed comparing ID in older populations to those with paediatric onset.

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    Understanding Significance Of Low Level Mosaicism In Rare Paediatric Disease Associated With Intellectual Disability And Autism


    In the last five years the diagnosis of rare genetic diseases has been revolutionised by new DNA sequencing technologies. However, even after state-of-the-art genetic testing a specific cause remains elusive for more than half of affected children. In some individuals with a genetic disorder, the mutation that causes the disease is only present in a minority of cells of the body. This phenomenon, called mosaicism, can make standard genetic testing techniques ineffective resulting in missed diagnoses. Mosaicism may also be responsible for atypical and/or milder features of these disorders, which could mean that doctors may not recognise the features that should trigger appropriate genetic testing. This could result in long delays in coming to the right diagnosis, with lost opportunities for early treatment and for accurate reproductive advice for the families. This project will focus on understanding of clinical and molecular significance of low level mosaicism across leading rare paediatric diseases associated with intellectual disability and autism including fragile X, Prader-Willi and Angelman syndromes. The work will be conducted as part of a large multidisciplinary team involving molecular genetics / genomics, clinical genetics, child psychology, neuroscience and bio-statistics expertise, with appropriate interdisciplinary training provided. The project will involve laboratory and clinical data collection and analyses on already recruited national and international cohorts. 
    The project with aim to understand:
    1. How does mosaicism impact current rare disorder prevalence estimates, and our understanding of disorder natural history, and patient stratification?
    2. How does prevalence of mosaicism for genetic mutations compare in asymptomatic children from the general population to cohorts of affected children referred for diagnostic testing? 
    3. How sensitive should molecular techniques be to be clinically meaningful?
    While there is flexibility on whether the focus is primarily laboratory or clinical, preference will be given to candidates with interest and/or background in bioinformatics. 

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    Ethics Of Implementing Genomic Sequencing In Routine Newborn Screening 

    Please contact christopher.gyngell@mcri.edu.au, danya.vears@mcri.edu.au and lauren.notini@mcri.edu.au for more information.  

    Since routine newborn screening began in the 1960s, it has become an important and effective health initiative to identify and significantly decrease morbidity and mortality in asymptomatic babies with rare disorders. Historically, the selection of conditions to be screened has been limited to those conditions where, if left untreated, newborns would suffer from severe illness, and where early intervention carries definitive medical benefit. The advent of a new type of testing, next-generation sequencing, now allows the entire genome to be sequenced at once. This genomic sequencing therefore has the potential to revolutionize newborn screening, allowing for more conditions to be screened. However, use of NGS in newborn screening would carry technical challenges and limitations, and would not remove the need for concurrent biochemical testing in order to screen for all the conditions currently offered by newborn screening programs. It may also threaten society's conceptualization of the public health goals of newborn screening programs and the focus on the best interests of the child.

    This research project aims to explore a variety of stakeholders' opinions on the ethical and social issues relating to the implementation of new genetic technologies in newborn screening programs in Australia, and to influence development and further refinement of policies in this area.

    This project would involve two main components:
    1. Assessment of the current professional recommendations and practical considerations regarding the implementation of next-generation sequencing in newborn screening programs. This would involve systematic literature searches and content analysis of relevant professional guidance documents.
    2. Exploration of stakeholders' views on the ethical and social implications of implementation of next-generation sequencing technologies into newborn screening programs. This would involve qualitative interviews, and potentially a survey, with relevant stakeholders, such as health professionals and/or prospective parents.

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    Solving Rare Diseases Via The Australian Genomics Mitochondrial Disease Flagship

    A "rare disease" affects fewer than 1/2000 people but there are over 7000 rare diseases that collectively affect 5% to 10% of the population, many of whom suffer life-threatening diseases or lifelong chronic disease. Rare diseases are thus a major public health problem and affected families have often faced a long diagnostic odyssey in attempting to achieve a diagnosis. Australian Genomics is a collaboration of over 40 Australian centres seeking to translate new genomic technologies into improved outcomes for rare diseases and cancer. Mitochondrial (mito) diseases are one of the first flagship projects. They are the most common group of inherited metabolic disorders and highly complex since they comprise almost 300 different genetic disorders with a wide range of clinical phenotypes and types of inheritance. 

    In previous studies we have used whole exome sequencing or whole genome sequencing to achieve diagnostic yields of over 60% in retrospective cohorts, identifying over a dozen novel disease genes. This project will focus on a prospective national cohort of paediatric patients who fit entry criteria for having probable mitochondrial disease. Recruitment commenced in early 2017, with half the cohort having whole genome and half whole exome sequencing over a 2-year period. Some patients will have sequence variants identified that have been previously shown to cause disease, which are straightforward to classify. Others will have novel sequence variants identified in known disease genes or in candidate disease genes not previously linked to disease. The project will use a range of bioinformatic, molecular, biochemical, immunochemical and cell biology approaches to investigate causality of novel variants. This will contribute to obtaining definitive diagnoses in previously unsolvable cases, understanding pathogenic mechanisms of disease and developing methods that can be applied to understanding the genetics of a wide range of other rare diseases.

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    Examining A New Drug Target For Preventing Stomach Cancer

    Stomach cancer (gastric adenocarcinoma) is the fifth most common cancer in the world and the third leading cause of death due to malignancy. The vast majority of these cancers develop as a direct result of a chronic gastritis (inflammation of the stomach) caused by infection with the spiral-shaped bacterium Helicobacter pylori. These bacteria inhabit the specialised niche of the human stomach lining, where they infect approximately half the world's population. Infection with this pathogen drives an inflammatory response that lasts for decades; it is this inflammation which is the key driver in the development of stomach cancer. 
    We have identified a genetic polymorphism that considerably increases the chance of someone infected with H. pylori developing stomach cancer. This gene encodes a receptor expressed on the cell surface and when activated can modify the inflammatory response to bacteria. Moreover, drugs are already available that can modify the activity of this receptor.
    This PhD project firstly aims to examine the polymorphism of this gene in order to understand how it modifies the activity of the receptor and thereby make some people more susceptible to cancer. Secondly it aims to examine the potential use of drug treatment in reducing H. pylori induced inflammation and thereby developing a novel treatment for preventing the development of stomach cancer. 

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    Adult Pneumonia In Mongolia In The Era Of A Childhood Pneumococcal Vaccine Programme

    The project in Mongolia will explore how the introduction of the pneumococcal conjugate vaccine (PCV) into the routine immunisation programme in children has impacted adult respiratory disease in the country. It will also explore other risk factors for adult pneumonia including the impact of air pollution and will provide the Government of Mongolia with additional information regarding the full impact of PCV in the country. 
    Prior experience in public health, epidemiology or a related discipline and a high academic standard of achievement are required. An interest in international child health and vaccinology would be viewed positively.
    The position will be based at the Murdoch Children's Research Institute, Melbourne. 

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    Streptococcal Transmission And Disease

    The bacterium Streptococcus pyogenes (group A streptococcus, "Strep A") causes a range of mild to severe infections, ranging from sore throat to streptococcal toxic shock syndrome. Importantly, S. pyogenes infections can lead to serious sequelae such as rheumatic fever and rheumatic heart disease. S. pyogenes can also colonise a variety of human tissues including the upper respiratory tract and skin in healthy people.

    In a related bacterial species, Streptococcus pneumoniae, we have shown that viral co-infection can enhance bacterial virulence by increasing bacterial density and inflammation in the host, and by driving changes in expression of bacterial virulence genes. There is recent clinical epidemiologic evidence that viruses are also important in S. pyogenes pathogenesis, but little is known about this process.

    In this project, you will use a murine model of S. pyogenes colonisation to examine the effect of viruses on S. pyogenes colonisation, transmission (spread to co-housed littermates) and disease, and the mechanisms involved. To achieve these aims, a range of methods will be employed including animal and tissue handling, immunological assays, traditional microbiology and molecular approaches such as qPCR, and gene expression analyses. Your project will provide important novel data on key components of S. pyogenes pathogenesis, and inform a pathway towards improving strategies for preventing S. pyogenes infections.

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    Virulence Genes In Streptococcus Pneumoniae

    Streptococcus pneumoniae (the pneumococcus) is a leading cause of pneumonia in children world-wide. This bacterium asymptomatically colonises the upper respiratory tract, but can transition to a pathogenic state to cause disease in the lower respiratory tract. We are interested in identifying the genetic factors that trigger this transition and have identified a putative genes we hypothesise may play a role in this process. 
    In this molecular microbiology project, your aim is to elucidate pneumococcal pathogenesis. You will create pneumococcal mutant strains in which the genes are deleted or overexpressed. The transcription of these genes will be examined, including in clinical samples. The role of these genes in virulence of these genes will be confirmed in models of pneumococcal pathogenesis. Key approaches include: genetic manipulation of pneumococcal strains, experiments with DNA, RNA and proteins; as well as conducting functional assays in vitro and/or in vivo.

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    Rare Opportunity For A PhD Project In Rural West Africa

    A rare opportunity for a PhD project is open in rural West Africa. A large cluster-randomised trial of an alternative compared to standard schedule of pneumococcal conjugate vaccine (PCV) will soon begin in The Gambia. The trial is based at the well-established UK Medical Research Council (MRC) Unit The Gambia at London School of Hygiene & Tropical Medicine. The Unit has conducted a number of large vaccine trials that have influenced global policy, including trials of PCV, meningococcal and Hib vaccines. The duration of the trial is 4.5 years with ample time to complete a PhD, which could be focused on a range of questions related to the trial: clinical, microbiological, epidemiological. Murdoch Children's Research Institute (MCRI) is a key collaborator in the trial. PhD supervision would be provided by investigators in the MCRI Pneumococcal group, including Dr Grant Mackenzie, who is seconded permanently to MRC in The Gambia.

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    Pathogenesis Of Pneumococcal Pneumonia

    Streptococcus pneumoniae (the pneumococcus) is the most common cause of community-acquired pneumonia and a leading killer of children world-wide. However, it is also commonly found as an asymptomatic coloniser of the upper respiratory tract, particularly in children. We are interested in elucidating the molecular processes by which the pneumococcus can transition from the carriage to infection state, and identifying signals of pneumococcal pneumonia. Previous work in our laboratory using clinical samples collected from children in The Gambia, West Africa, hospitalised with pneumonia has identified several pneumococcal genes that were upregulated in the lung. 
    Your project will have two main aims: to elucidate the role of these genes in pneumococcal pneumonia, and to examine pneumococcal gene expression in samples collected from pneumonia patients at the Royal Children's Hospital. You will use a variety of approaches to identify and characterise pneumococcal genes and proteins involved in pneumococcal pneumonia. This includes genetic manipulation of pneumococci, functional assays to characterise bacterial mutants, and measurement of gene and protein expression using methods such as qRT-PCR, RNA-seq, western blotting, and ELISA. 
    Access to clinical samples such as pleural fluid provides the unique opportunity to examine pneumococcal gene expression during pneumonia. This project will provide exciting new data on the pathogenesis of pneumococcal pneumonia.

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    Filling In The Gaps: Antimicrobial Use, Misuse And Resistance In Children

    Antimicrobial resistance (AMR) is the greatest global healthcare crisis of our time. Antibiotics underpin modern healthcare and are threatened by the spread of resistance. Half of all Australian children are given at least one course of antibiotics by their first birthday - one of the highest rates in the world. Despite this, research into children is this area is lacking and there are fundamental knowledge gaps around antimicrobial use, resistance and their relationship. Prospective PhD students will have the opportunity to investigate a research question of interest, focussing around broader themes of:

    Mapping AMR in children: We do not know the current prevalence of AMR in children. Projects in this area will investigate AMR prevalence in different child populations in hospital and in the community, explore how use relates to AMR and the impact of other factors (socio-economic status, hospitalisation). There are also project opportunities to investigate the effects of antibiotics on the overall bacterial make-up (the microbiome) in early childhood.

    Improving antimicrobial prescribing and health services: electronic medical records provide a rich source of patient-centred clinical data. Projects in this area will focus on how to best use these large amounts of information to link actions (e.g. prescribing) to outcomes (e.g. readmission, adverse events) and to design clinical interventions to target problem areas. 

    Right person, right time, right place: It is well known that children do better at home than in hospital and delivering intravenous antibiotics at home is increasing. There is, however, very little evidence on the best and safest ways to do this. Projects in this area will focus on clinical trials of intravenous antibiotic use at home for different childhood infections, incorporating quality of life and health economic measures. Projects will also investigate whether traditional ways of giving antibiotics can be manipulated to improve their usefulness.

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    Restacking The Odds: Understanding The Barriers And Solutions To Antenatal Care Participation

    Restacking the Odds project is a project being undertaken by a partnership between the Murdoch Children's Research Institute, Social Ventures Australia and Bain & Company. It aims to reduce intergenerational disadvantage by creating a set of metrics and tools that can help drive a reconfiguration of the existing service system through an equity and evidence lens; driving changes that result in the best quality services reaching the most disadvantaged areas of Australia. Too many children are born into circumstances that do not provide them with a reasonable opportunity to make a good start in life. For some, this experience is part of a persistent cycle of inter-generational disadvantage which their parents also experienced. 
    Currently there is a lack of data and evidence available to guide efforts to reduce the disadvantage experienced by many Australian children. Large amounts of money, and significant social sector effort, are applied without the benefit of evidence (or impact) that would be considered fundamental in other arenas. 
    Restacking the Odds aims to help accelerate improvement in the disadvantaged circumstances faced by too many of Australia's children. The project includes foundational work to create an actionable, evidence-based framework to provide practical guidance to policy-makers, service delivery organisations and communities in the effective design and delivery of their work to address the needs of disadvantaged children and their families. This framework can then be applied more broadly.
    A supporting piece of work relates to the core Restacking the Odds project and we a seeking a PhD or Masters student to do a deep-dive.

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    Nature Vs Nurture: What Are The Key Genetic Drivers Of Bone Health And How Does The Environment Modulate Their Effect?

    The underpinnings of health outcomes in non-communicable diseases remains the subject of debate and further studies. In particular, developing a greater understanding of the interaction between genetic predisposition ("nature") and lifestyle factors ("nurture") is crucial to prevention and treatment of these conditions. Optimizing bone health is a key issue in minimizing long term morbidity, given the significant negative effects of osteoporosis and fragility fractures on individuals and the community as a whole.

    Bone health outcomes are known to be strongly hereditary, with population studies assisting in expanding our understanding of which genes are driving the development of optimum bone mass and strength, and how they interact with environmental factors. The child health CheckPoint, a cross sectional health screen of 11-12 yr olds and one of their parents, which is embedded within the longitudinal study of Australian children (LSAC) cohort, provides a unique dataset to further explore these questions. Cross sectional bone data from peripheral quantitative computed tomography (pQCT) scanning taken during CheckPoint of subjects and parents can be explored in conjunction with DNA in order to explore previously identified genes, and how they interact with the various components of the bone scan, including skeletal geometric parameters, bone density and bone strength. The differential effects on the cortical and trabecular compartments can also be explored.
    Using the lifestyle data from the CheckPoint study, and longitudinal data from the LSAC study, the interactions between the genetic and environmental factors can be assessed, with available data including diet, activity, sun exposure, maternal health in pregnancy,medications, demographics, smoking/ alcohol history, sleep. 

    The PhD candidate will be running these key analyses and using these results to develop further hypotheses that can explored using the extensive data set. This project is available to students able to attract funding stipends (eg via the university or international scholarships).

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    Prenatal Plastic Product Chemical Exposure And Adverse Obesity And Cardiovascular Outcomes In Offspring: The Barwon Infant Study. 

    There is increasing public health concern about the environmental and health effects of plastic product chemicals such as bisphenols and phthalates that are now much more common in pregnant women and children. Mounting evidence suggests that in utero and early postnatal period exposure to these environmental chemicals may be associated with an increased risk of obesity, early atherosclerosis and other markers of cardiovascular risk among children. In the unique Barwon Infant Study (BIS) of 1000 mothers and their children (www.barwoninfantstudy.org.au/), we have found that almost all pregnant women harbour these chemicals and that the associated adverse health effects may be particularly evident among children at genetic risk of oxidant damage. BIS has environmental measures and biospecimens with genome-wide genetic data already collected from mid-gestation to age 4 years. The overall aims of this project are to examine the association between higher prenatal plastic product chemical measures and longitudinal measures of adiposity and cardiovascular health in the subsequent offspring from birth to age 4 years. The availability of genome-wide SNP data will allow the assessment and reporting of gene-environment interactions. This project will contribute to public health policy on plastic product chemical exposure during pregnancy and may contribute to the identification of those at greater genetic vulnerability to plastic pollutant-induced health effects. This project may be supported by LifeCourse. Visit http://lifecourse.melbournechildrens.com/for-students/ for more information.

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    Outcomes of childhood hearing loss at a population level

    Background: Universal newborn hearing screening, cochlear implantation, and sophisticated amplification have secured remarkable gains in hearing impaired children's life chances. However, mean language/vocabulary/reading outcomes of these children in the early school years are still 0.7-0.9 standard deviations below those of their hearing peers and below their own cognitive potential. There is limited understanding of why this is the case, despite early access to hearing technology and services. In particular, children with mild hearing loss have not seemed to benefit from earlier diagnosis. There is a need to identify when and how to best intervene to optimise outcomes for children with hearing loss.

    Aims: Using data from a unique population-based longitudinal databank of children with hearing loss to:
    1)Understand when delays in language development become apparent by examining secular trends in outcomes
    2)Determine the early predictive factors of later language outcomes
    3)Examine the impact of device use and early intervention on later language outcomes

    Methods:
    The Victorian Childhood Hearing Impairment Longitudinal Databank (VicCHILD) is a whole-of-state population databank of children with permanent hearing loss, with >750 participants, making it the world's largest longitudinal databank of its kind. It has >95% of families consenting to data linkage and further research, and >90% providing biosamples for genetic analyses. VicCHILD has close collaborations with the Victorian Infant Hearing Screening Program (VIHSP), the Caring for Hearing Impaired Children Clinic (CHIC), and the Melbourne Genomics Health Alliance through which whole exome sequencing was available in 2016/17. VicCHILD collects audiological, phenotypic, socio-demographic, quality of life and health services data at baseline, and outcomes data at key developmental stages (2, 5-7, 9-12 years). The PhD student will explore this rich and unique dataset, and contribute to its data collection, to achieve the aims.

    This project may be supported by LifeCourse. Visit http://lifecourse.melbournechildrens.com/for-students/ for more information

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    Do Targeted Newborn Screening And Early Antiviral Therapy Prevent Sensorineural Hearing Loss Due To Congenital Cytomegalovirus Infection (Ccmv)?


    Background: cCMV is believed to account for 15-20% of bilateral moderate to profound sensorineural hearing loss (SNHL), and can cause multi-organ failure, poor growth and neurodevelopmental sequelae. International studies suggest approximately 0.6 % of live births are infected with cCMV. Two recent RCTs have shown antiviral therapy for symptomatic cCMV within one month after birth to reduce SNHL progression and improve neurodevelopmental outcomes. However, these trial results only apply to infants with severe brain involvement with cCMV, and not isolated SNHL, with early institution of antiviral therapy. We need to develop mechanisms to provide expedited newborn screening of infants for cCMV and enable recruitment of infants with hearing loss and cCMV into clinical trials of antiviral therapy. 

    Aims: 
    1) To determine the feasibility and cost effectiveness of targeted newborn screening for cCMV screening in Victoria, 
    2) To determine the prevalence and natural progression of SNHL and development in Australian children with cCMV (using Victorian longitudinal cohorts), and 
    3) To develop a framework for evaluation of the benefit and harms of early antiviral therapy for cCMV in infants with SNHL in Australia.

    Methods:
    Aim 1: Feasibility and cost-effectiveness study of salivary swab PCR testing followed by antiviral treatment if cCMV positive in newborn infants referred with two failed hearing screens. 

    Aim 2: Longitudinal cohort of infants with cCMV referred to audiology after two failed hearing screens, based on Aim 1.

    Aim 3: Development of an appropriate framework or trial to evaluate benefits and harms of early antiviral therapy for cCMV in infants with SNHL.

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    How Do Primary Schools Support The Mental Health Of Students: Gathering The Evidence To Align Practice To Evidence

    The 2016 Young Minds Matter report found 14% of 4-11-year-old Australian children meet the criteria for a mental health difficulty, with only half accessing support services. The nearly universal reach of the education system enables schools to play an important role to support children with mental health difficulties, and prevent the development of disorder in others. Schools around Australia offer numerous mental health programs and interventions. However, there is no systematic understanding of what is being offered or the impact of these interventions.

    Although some school mental health interventions have a strong evidence base, limited research has examined what schools are actually implementing to understand the gap between evidence and practice. This will inform the extent schools need support to implement evidence-based interventions and also identify interventions that schools are implementing that need robust evaluation.

    This study will establish a snapshot of mental health interventions currently being provided during the first three years of primary school in Victoria, examining:
    1. What interventions and programs are schools implementing?
    2. How are they being implemented?
    3. The extent these interventions align with evidence-based practice?

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    Understanding Current School-Based Interventions For Students With Reading Difficulties In The Early Years Of Primary School

    In Australia, 1 in 10 children have severe difficulties with reading, commonly referred to as 'dyslexia' or Specific Reading Difficulties. Internationally, these children are characterised by their difficulty learning to read, despite the provision of appropriate, conventional instruction, adequate intelligence, and adequate sociocultural opportunity. The reading difficulties associated with dyslexia are neurological in origin, permanent in nature and resistant to intervention, though with appropriate help children can develop compensatory skills. Despite the potential for improving the academic and mental health outcomes for these children during the early years of school, there is no Australian data on what interventions schools currently provide or the evidence these interventions have. 

    This study will aim to systematically understand the interventions provided during the first three years of primary schooling to support children with severe reading difficulties. The way in which these interventions are implemented will also be examined, including: 
    a. who receives the intervention (target population)
    b. how much the intervention costs
    c. where funding to provide the intervention is sourced from 
    d. how strong the evidence base is for the intervention

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    Optimising Diagnostic Testing For Tree Nut Allergy

    Tree nut allergy in children is common, often serious and usually life-long. Recent data from the Health Nuts study (MCRI) has found prevalence of tree nut allergy at age 6 to be as high as peanut allergy (3.1%). However, despite a plethora of research into peanut allergy, there is an evidence-practice gap in the prevention, diagnosis and treatment of tree nut allergy.

    Current diagnosis of tree nut allergy is based on clinical history and skin prick testing (SPT). SPT has a high sensitivity but low specificity and is therefore unable to determine in those without a history of a reaction, clinical allergy or tolerance; necessitating specific nut elimination or oral food challenge. 

    The HealthNuts study is the world's largest population-based, longitudinal study of food allergy and in early childhood. 5300 12-month old infants had skin-prick testing, and those with a positive test proceeded to hospital-based food challenges to assess for food allergy. The cohort has been followed up at ages 4 and 6 years and an age 10-year follow-up is underway. Therefore ethically approved samples of plasma, peripheral blood mononuclear cells and granulocytes from tree nut allergic and tolerant children are in storage and available for analysis. 

    This project will combine immunological and epidemiological risk factors to improve diagnostic and prognostic prediction of tree nut allergy. Using samples from the HealthNuts study, novel laboratory techniques for use in screening, determining severity and reaction thresholds for tree nut allergy will be explored. Some of the methods will include serological tests such as component-resolved diagnostics and cellular assays such as basophil activation tests and single cell flow cytometry. 

    Findings from this study will have significant clinical implications, as less invasive tests will avoid risk of adverse reactions through and oral food challenge and improve patient management with the prediction of prognostic outcomes.

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    Handling Missing Data In Complex Longitudinal Studies

    Missing data are inevitable in epidemiological studies. If not handled appropriately, missing data can affect the validity and accuracy of the results from such studies. Multiple imputation has become a popular approach for dealing with missing data, however as research studies become more complex there is a need to expand the current methodology and determine whether multiple imputation is indeed the best approach. This PhD project will evaluate and develop approaches for handling missing data in the context of complex longitudinal studies. This will be achieved through a combination of simulation studies and detailed case studies answering important epidemiological questions.

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    Brain structure and function in paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME)

    Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a debilitating condition with unknown aetiology that results in considerable functional disability during a critical phase of development. Disturbed brain structure and function is currently a leading hypothesis in the search for a pathophysiological mechanism behind CFS/ME. However, we have  limited understanding of the nature of brain dysfunction in paediatric CFS/ME in comparison with typical adolescents, and whether brain abnormalities might be able to predict long-term outcomes (i.e., cognition, fatigue, daily functioning, sleep quality, mental health, clinical status). This longitudinal research project will employ the use of state-of-the-art multi-modal MRI data (structural MRI, diffusion-weighted MRI, resting-state functional MRI, magnetic resonance spectroscopy) in order to:

    1. Examine differences in brain structure and function over the course of the CFS/ME illness in CFS/ME adolescents compared with healthy adolescent controls
    2. Study brain-behaviour relationships in normal development, and in paediatric CFS/ME
    3. Predict long-term clinical and functional outcomes in paediatric CFS/ME

    Due to the rich data collected in this longitudinal project, there is great opportunity for students to choose a research question that interests them.

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