our values - telethon kids institute...our goal is to build on our success and create a research...

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Telethon Kids Institute is the largest medical research facility in Western Australia. With more than 600 staff and students, we are also one of Australia’s largest research facilities dedicated to child health. Our multidisciplinary approach brings together clinical researchers, laboratory scientists and epidemiologists all under the one roof to tackle the many complex childhood diseases and issues from a range of different angles. Our goal is to build on our success and create a research institute that makes a real difference in our community, which will benefit children and families everywhere. We will do this together, with our values underpinning the way we work and make decisions.

OUR VALUES

COLLABORATION COURAGE EVIDENCE RESPECT

Our work is better when we work together

No problem is too big or too difficult

We do not compromise on quality

We are honest, ethical, and fair

CHRONIC AND SEVERE DISEASES

Chronic and Severe Diseases is a Research Focus Area (RFA) which focuses on diseases in children that require a very different investigation and treatment to similar conditions in adults. Childhood cancers, diabetes, respiratory conditions and rare diseases can be debilitating and often life threatening. Effective intervention and prevention requires an understanding of the complex interactions between genetic and environmental factors, as well as a focus on better ways of diagnosing, treating and controlling disease at the individual and population level. Research Programs & Teams listed:

• Cancer o Brain Tumour Research o Cancer Immunotherapy o Leukaemia and Cancer Genetics o Oncogenic Signalling Laboratory

• Diabetes & Obesity o Cardiometabolic Sunhealth o Diabetes and Obesity Research

• Genetics and Rare Diseases o Genetics and Health

• Respiratory Health o Airway Epithelial Research o Children’s Lung Health o Children’s Respiratory Science Group o P4 Respiratory Health for Kids

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TABLE OF CONTENTS

CANNABINOIDS FOR THE TREATMENT OF CHILDHOOD BRAIN CANCER ............................................................... 5

FINDING NEW TREATMENTS EFFECTIVE AGAINST PAEDIATRIC BRAIN CANCER ..................................................... 6

HARNESSING THE IMMUNE SYSTEM TO ENHANCE TREATMENT EFFICACY AND IMPROVE SURVIVAL OUTCOMES FOR

BRAIN CANCER ......................................................................................................................................... 7

IDENTIFYING PREDICTIVE IMMUNE BIOMARKERS OF ANTI-CANCER IMMUNITY .................................................... 8

IMPROVING CELLULAR THERAPY FOR THE TREATMENT OF CANCER .................................................................... 9

THE BONE MARROW MICROENVIRONMENT DURING LEUKAEMOGENESIS ........................................................ 10

IDENTIFICATION OF NOVEL DRUG COMBINATIONS TO CURE HIGH-RISK INFANT LEUKAEMIA ............................... 11

IMPACT OF COPY NUMBER AMPLIFICATIONS IN PAEDIATRIC ACUTE LEUKAEMIA ................................................ 12

AGGRESSIVE BRAIN CANCER: DETERMINING THE ROLE OF ERBB4 ................................................................... 13

REPURPOSING ION CHANNEL DRUGS TO SENSITIZE DIFFUSE INTRINSIC PONTINE GLIOMA TO TARGETED THERAPIES 14

UNDERSTANDING THE FUNCTION OF ION CHANNELS IN HIGH GRADE GLIOMA .................................................. 15

EXPLORING HOW ONGOING EXPOSURE TO LOW DOSE ULTRAVIOLET RADIATION PREVENTS WEIGHT GAIN AND

SUPPRESSES THE DEVELOPMENT OF TYPE-2 DIABETES .................................................................................. 16

TESTING THE CAPACITY OF AN ONLINE TOOL TO PROMOTE SAFE SUN BEHAVIOURS IN TEENAGERS ...................... 17

CO-DEVELOPING AND TRIALLING AN INTERVENTION TO HELP TEACHERS AND COACHES SUPPORT CHILDREN AND

ADOLESCENTS WITH TYPE 1 DIABETES WHEN PHYSICALLY ACTIVE ................................................................... 18

DEVELOPING AND TRIALLING A PEER SUPPORT PROGRAM FOR STUDENTS WITH TYPE 1 DIABETES IN SCHOOLS ...... 19

DEVELOPING EDUCATIONAL RESOURCES FOR SPORTS COACHES AND TEACHERS TO SUPPORT CHILDREN AND

ADOLESCENTS WITH TYPE 1 DIABETES BE PHYSICALLY ACTIVE ........................................................................ 20

EFFECT OF HIGH BLOOD GLUCOSE LEVELS ON EXECUTIVE FUNCTION, ATTENTION AND DRIVING PERFORMANCE ON A

DRIVING SIMULATOR IN PEOPLE WITH TYPE 1 DIABETES ............................................................................... 21

EFFECT OF SWIMMING AND HEAD-OUT WATER IMMERSION IN COLD WATER ON THE RISK OF HYPOGLYCAEMIA IN

TYPE 1 DIABETES .................................................................................................................................... 22

EFFECT OF HYPOXIA TYPICAL OF HIGH ALTITUDE ON THE ACCURACY OF CONTINUOUS GLUCOSE MONITORS AND ITS

IMPACT ON BLOOD GLUCOSE MANAGEMENT IN INDIVIDUALS WITH TYPE 1 DIABETES MELLITUS ......................... 23

HOW DOES MODE OF DELIVERY INFLUENCE RISK OF CHILDHOOD TYPE 1 DIABETES IN WESTERN AUSTRALIA? ...... 24

HOW IS MATERNAL VITAMIN D SUFFICIENCY DURING PREGNANCY ASSOCIATED WITH THE RISK OF ISLET

AUTOIMMUNITY DEVELOPMENT IN CHILDREN AT RISK OF TYPE 1 DIABETES? ................................................... 25

IMPACT OF FOOD ON GLYCAEMIC CONTROL IN INDIVIDUALS WITH TYPE 1 DIABETES ......................................... 26

IS THE RECOMMENDATION TO DECREASE BASAL INSULIN DOSE PRE-EXERCISE CONDUCIVE TO SEVERE

HYPERGLYCAEMIA DURING AND AFTER EXERCISE? ....................................................................................... 27

MANAGING TYPE 1 DIABETES DURING EXERCISE – A DESCRIPTIVE STUDY OF COMPETITIVE ATHLETES WITH TYPE 1

DIABETES............................................................................................................................................... 28

NEGOTIATING THE PATH TO SELF-MANAGEMENT OF T1D – ADOLESCENTS’ AND PARENTS’ PERSPECTIVES ........... 29

USING CONTINUOUS GLUCOSE MONITORING AND A CARBOHYDRATE ALGORITHM TO MANAGE BLOOD GLUCOSE

LEVELS DURING EXERCISE IN ADOLESCENTS WITH TYPE 1 DIABETES ................................................................. 30

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RAPID DIAGNOSIS OF RARE GENETIC DISEASES IN PAEDIATRIC PATIENTS .......................................................... 31

AUTOMATED ANALYSIS OF CLINICAL LUNG SAMPLES THROUGH MACHINE LEARNING ......................................... 32

ESTABLISHING THE LUNG VIROME PROFILES IN CYSTIC FIBROSIS CHILDREN WITH AND WITHOUT EXACERBATIONS ... 33

EXPLORING THE THERAPEUTIC POTENTIAL OF PHAGE THERAPY TO TREAT LUNG INFECTIONS IN CHILDREN WITH

CYSTIC FIBROSIS ..................................................................................................................................... 34

INVESTIGATING THE ROLE OF EPITHELIAL-FIBROBLAST CROSS-TALK IN LUNG FIBROSIS ....................................... 35

PERSONALISED CFTR THERAPY SCREENING USING A GENETICALLY MODIFIED, PRIMARY AIRWAY EPITHELIAL CELL

BASED HIGH‐THROUGHPUT SCREENING ASSAY ............................................................................................ 36

SCREENING AMNIOTIC EPITHELIUM ........................................................................................................... 37

ASSOCIATIONS BETWEEN DISEASE PROGRESSION AND QUALITY OF LIFE IN CHILDREN WITH NEUROMUSCULAR

DISORDERS ............................................................................................................................................ 38

CAN A SHORT TRIAL OF FLIXOTIDE IN CHILDREN WITH AIRWAY INFLAMMATION IMPROVE OUTCOMES AFTER ENT

SURGERY? ............................................................................................................................................. 39

DEVELOPING CLINICAL PREDICTORS OF DISEASE PROGRESSION IN CHILDREN WITH ............................................ 40

NEUROMUSCULAR DISORDERS TO PREVENT FUTURE RESPIRATORY FAILURE ..................................................... 40

DEVELOPING CLINICAL PREDICTORS OF DISEASE PROGRESSION IN CHILDREN WITH NEUROMUSCULAR DISORDERS TO

PREVENT FUTURE RESPIRATORY FAILURE .................................................................................................... 41

EXPLORING THE EFFECTS OF PRETERM BIRTH ON THE AIRWAY EPITHELIUM ...................................................... 42

FORCED OSCILLATION TECHNIQUE: CLINICAL UTILITY OF WITHIN-BREATH ANALYSIS ......................................... 43

GLOBAL LUNG FUNCTION INITIATIVE (GLI): DERIVING GLOBAL MULTI-ETHNIC REFERENCE VALUES FOR THE

MEASUREMENT OF LUNG FUNCTION ......................................................................................................... 44

IMAGING THE LONG-TERM EFFECTS OF PRETERM BIRTH ON THE LUNG ........................................................... 45

PERSONALISED, MACHINE LEARNING BASED PREDICTION OF ASTHMA AND ALLERGIES IN WESTERN AUSTRALIA ..... 46

PREDICTING LONG-TERM HEALTH OUTCOMES IN YOUNG ADULTS BORN VERY PRETERM (WALHIP 19-YEAR

FOLLOW-UP) ......................................................................................................................................... 47

UNDERSTANDING ASTHMA AND RESPIRATORY HEALTH IN URBAN AND REGIONAL AREAS OF WESTERN AUSTRALIA 48

AETIOLOGY OF CHILDHOOD ACUTE ASTHMA ............................................................................................... 49

ADVANCED ANALYSIS OF CT SCANS OF LUNG DISEASE .................................................................................. 50

ARTIFICIAL INTELLIGENCE TO DIAGNOSE LUNG INFECTION AND PROVIDE PROGNOSIS ON CT SCANS IN CYSTIC

FIBROSIS ................................................................................................................................................ 51

AUTOMATED TRACKING OF EPITHELIAL CELL MIGRATION .............................................................................. 52

VALIDATION OF LUNG MRI AS A CLINICAL ENDPOINT IN CYSTIC FIBROSIS ......................................................... 53

NOTES .................................................................................................................................................. 54

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Cannabinoids for the Treatment of Childhood Brain Cancer Research Program Cancer Research Group Brain Tumour Research Start Date Flexible, available immediately Chief Supervisor Dr Raelene Endersby (Telethon Kids Institute) Other Supervisors Dr Clara Andradas Arias (Telethon Kids Institute) Project Outline Brain tumours are the leading cause of disease-related death in children and are among the most

challenging childhood cancers to treat. The standard treatment consists of surgery followed by radiotherapy and chemotherapy. Despite the aggressiveness of the treatment, the overall survival rates for these patients have not improved for decades, and its impact is devastating, producing long-term sequelae in survivors. Thus, there is an urgent need to identify more effective therapeutic strategies. Over the last decades, a large body of evidence has demonstrated that active compounds from the plant Cannabis sativa, called cannabinoids, exhibit anti-cancer effects in different cancer types and in a wide variety of experimental models of cancer, ranging from cancer cell lines, xenografted animals to genetically engineered mouse models. Despite evidence demonstrating the anti-tumour properties of cannabinoids in adult cancers, there is very little data about the effect of these compounds on paediatric cancers. In particular, there is no existing data in paediatric brain tumour models. Our laboratory has generated a solid research pipeline using innovative tools to test new drugs in paediatric brain tumours that can predict what could happen in patients. We use sophisticated laboratory models, with state-of-the-art imaging and therapeutic delivery equipment that closely mimic treatment of the human disease. Using this research pipeline, we are evaluating the anti-cancer effects of cannabinoids alone or in combination with traditional chemotherapy or radiation therapy, both in vitro and in vivo, to understand their mechanisms of action in paediatric brain tumours. Over the course of the project, the student will develop expertise in

• Tissue culture –aseptic technique, passaging & maintaining human brain cancer cell lines

• In vitro drug assays – determine if cannabinoids have anti-tumour effects and if they synergise with conventional chemo/radiotherapy

• Flow cytometry to assess cell cycle of human brain cancer cells

• Animal techniques: assist with implantation of brain cancer cells into the mouse brain; monitor mice after implantation for signs of a tumour; treat mice with chemotherapeutic drugs and cannabinoids.

• Histology such as paraffin sectioning and immunohistochemistry

• Biochemical techniques such as protein extraction and western blotting

Suitable For ☒ Honours ☐ MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Ability to work in a multi-disciplinary team

• Willingness to learn new skills and work with animals

• Good organisational skills

• Initiative and dedication For Honours/Masters candidates:

• Greater than credit average For PhD candidates:

• First-Class Honours degree or equivalent (e.g. Masters by Research) in biological discipline Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Clara Andradas Arias (08) 6319 1729 [email protected]

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Finding New Treatments Effective Against Paediatric Brain Cancer Research Program Cancer Research Group Brain Tumour Research Start Date Flexible, available immediately Chief Supervisor Dr Raelene Endersby (Telethon Kids Institute) Other Supervisors Dr Meegan Howlett (Telethon Kids Institute)

Dr Jaqueline Whitehouse (Telethon Kids Institute) Dr Clara Andradas Arias (Telethon Kids Institute) Dr Jessica Buck (Telethon Kids Institute)

Project Outline The Brain Tumour Research team at TKI is co-directed by Drs Nick and Raelene. The overarching goals of our group are to define the poorly understood basic biology of several types of childhood brain tumours and improve therapies. We achieve this in the following ways:

• Elucidate the molecular basis of different brain tumour types, including medulloblastoma and ependymoma among others, through the analysis of primary patient specimens.

• Improve understanding of the molecular events contributing to these diseases, by analysing the impact of altered signalling pathways on survival, proliferation, invasiveness and tumorigenicity of brain tumour cells.

• Develop novel preclinical models of paediatric brain tumours in which to test new treatments. We utilise transplantable xenograft, patient derived xenograft, and genetically engineered tumour models representative of paediatric brain tumour in our translational research.

• Obtain and test new therapies in combination with standard clinical chemotherapy and radiation protocols in appropriate brain tumour models. We acquired Australia’s first X-RAD SmART platform to model clinical radiation treatment and are currently investigating new therapies that can enhance its efficacy to hopefully reduce the toxic side-effects experienced by our patients.

• Translate our findings into improved therapies through clinical collaborations. We currently have project opportunities for a self-motivated and enthusiastic individual and invite you to meet with us to discuss specific projects. The student will develop expertise in a wide range of technologies including:

• Animal techniques


• Cell/tissue culture from mouse and human specimens

• Molecular techniques including DNA/RNA analysis, PCR and cloning

• Biochemical techniques such as protein extraction, western blotting and IP Students are expected to have excellent writing and oral presentation skills.


For Honours/Masters candidates:

• Distinction average or higher. For PhD candidates:

• First class Honours or equivalent (e.g. Masters by research) in biological discipline. *Medical undergraduates wishing to undertake a BMedSci may also be suitable. Students must be able to work relative independently in a multi-disciplinary team, willing to learn new skills and work with animals. We also expect great communication skills to both colleagues and the community, good organisational skills, initiative & dedication.

Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Raelene Endersby [email protected]

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Harnessing the Immune System to Enhance Treatment Efficacy and Improve Survival Outcomes for Brain Cancer Research Program Cancer Research Group Brain Tumour Research Start Date Flexible, available immediately Chief Supervisor Dr Raelene Endersby (Telethon Kids Institute) Other Supervisors Professor Terrance Johns (Telethon Kids Institute) Project Outline High Grade Glioma (including glioblastoma) is the most common brain cancer and can occur in

adults or children. Survivors of this disease are extremely rare, highlighting the urgent need for more effective therapies. Immunotherapy is an exciting new approach for treating cancer which harnesses the body’s natural defence mechanism: the immune system. While profound clinical benefits have been achieved in some cancers, this has not been the case in brain cancer. We need to be innovative in the way we use immunotherapy to treat brain cancers, and believe we have uncovered an exciting new angle. We are testing an immunotherapy that activates specialised immune cells in the brain called microglia. It works by blocking a signal called “CD47” that brain tumours use to hide from immune cells. Blocking CD47 makes brain cancers visible to immune cells, enabling them to attack and kill the tumour, resulting in significantly extended survival of mice with brain cancer. We first aim to enhance this immunotherapy by providing a second “hit” to further direct the immune cells to attack the cancer cells. We previously developed a glioblastoma-specific treatment, an “anti-EGFR antibody”. This antibody should make glioblastoma even more visible to the microglia, which we propose will further stimulate them to kill glioblastoma cells. Our second aim will determine if combining CD47-blockade with radiation is effective. Radiation is an essential component of brain cancer treatment and new treatments would need to be combined with radiation in the clinic; however, it is unknown how radiation will affect immunotherapy. We are uniquely placed to test this, as we have Australia’s first x-ray machine that mimics clinical radiation protocols in the laboratory. Our studies will utilise clinically-relevant brain cancer mouse models. Successful results will be developed into new clinical trials, with the ultimate goal of curing more brain cancer patients. The student will develop expertise in a wide range of technologies including:

• Animal techniques


• Cell/tissue culture from mouse and human specimens

• Biochemical techniques such as protein extraction, western blotting and IP Students are expected to have excellent writing and oral presentation skills.


For Honours/Masters candidates:

• Distinction average or higher. For PhD candidates:

• First class Honours or equivalent (e.g. Masters by research) in biological discipline. *Medical undergraduates wishing to undertake a BMedSci may also be suitable. Students must be able to work relative independently in a multi-disciplinary team, willing to learn new skills and work with animals. We also expect great communication skills to both colleagues and the community, good organisational skills, initiative & dedication.


☐ Full scholarship offered by project group For more information, please contact: Dr Raelene Endersby [email protected]

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Identifying Predictive Immune Biomarkers of Anti-Cancer Immunity Research Program Cancer Research Group Cancer Immunotherapy Unit Start Date March 2020 Chief Supervisor Dr Alison McDonnell (Telethon Kids Institute)

Dr Jason Waithman (Telethon Kids Institute) Other Supervisors Dr Bree Foley (Telethon Kids Institute) Project Outline Immunotherapy has revolutionised the treatment of cancer. These therapies aim to

amplify the anti-tumour T cell response to mediate improved cancer control. While remarkable responses have been observed in patients with advanced cancer, not all patients benefit from this treatment and immune related side effects can sometimes be observed. Our laboratory is focussed on understanding the anti-tumour T cell response in patients with cancer with an aim to better predict which patients will benefit most from treatment, and identify new immunotherapies for cancer. Some of our approaches include: Investigating how tumour-reactive T cells become activated to kill cancer cells Identifying immune biomarkers that help choose the right treatment for individual patients. We encourage all interested students to contact us and discuss specific project options. Techniques to be used:

• Human blood processing

• Flow cytometry

• Molecular biology


• Greater than credit average for Hons;

• BSc (Hons) or equivalent in biological discipline for Masters or PhD

• Good organisational skills, motivation and dedication Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Alison McDonnell (08) 6319 1212 [email protected]

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Improving Cellular Therapy for the Treatment of Cancer Research Program Cancer Research Group Cancer Immunotherapy Unit Start Date March 2020 Chief Supervisor Dr Bree Foley (Telethon Kids Institute)

Dr Jason Waithman (Telethon Kids Institute) Other Supervisors Dr Alison McDonnell (Telethon Kids Institute) Project Outline Our research program is focusing on developing new techniques and treatments for

treating children and adolescents with leukaemia. Whilst survival rates for childhood leukaemia have increased, it remains a leading cause of cancer-related deaths in children and adolescents. Exciting new treatments focused on harnessing the power of the immune system are altering the way oncologists approach the treatment of cancer. Redirecting T cells through the use of a chimeric antigen receptor (CAR) is revolutionising the treatment of refractory and relapsed leukaemia. Remarkable responses are being observed in some patients who had failed to respond to all conventional treatment options. However, these treatments, known as cellular therapy, are not working for everyone and our laboratory is focused on identifying novel and innovative approaches to ensure that more patients respond to this promising new therapy. These approaches include:

• Developing an improved therapy using T cells that will lower the risk of toxicity and lower the chance for the cancer cells to evade detection.

• Identifying ways to improve the durability of the immune cells used to make the cellular therapy.

• Develop an ‘off the shelf’ therapy that can be made from immune cells from healthy donors and used to treat patients with cancer.

We encourage all interested students to contact us and discuss specific project options. Techniques to be used:

• Cell culture

• Flow cytometry

• Molecular biology

• Small animal handling Suitable For ☒ Honours ☐ MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Greater than credit average for Hons;

• BSc (Hons) or equivalent in biological discipline for Masters or PhD

• Good organisational skills, motivation and dedication Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Bree Foley (08) 6319 1741 [email protected]

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The Bone Marrow Microenvironment during Leukaemogenesis Research Program Cancer Research Group Leukaemia and Cancer Genetics Start Date February 2020 Chief Supervisors Dr Laurence Cheung (Telethon Kids Institute, Curtin University)

Dr Rishi Kotecha (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors - Project Outline The tumour microenvironment is well documented to be a key factor in multiple stages of

cancer progression. It plays a particularly important role in resistance to therapy, relapse, and metastasis. While the tumour microenvironment in solid tumours has been intensely investigated, the importance of the leukaemia microenvironment has only recently been appreciated. Novel studies have demonstrated that the leukaemia microenvironment confers resistance in leukaemia, and that leukaemia cells usurp the normal haematopoietic microenvironment and are capable of altering the bone marrow microenvironment. However, the underlying mechanisms are not fully understood, and the bone marrow microenvironment of the most common childhood leukaemia has not been studied. With respect to children with this disease, bone marrow fibrosis correlates with worse survival, suggesting the importance of the bone marrow microenvironment in leukaemia progression. We have developed a model that enables the comprehensive investigation of the architecture of bone marrow microenvironment during leukaemia progression. This project will define in detail the changes of the bone marrow microenvironment during leukaemogenesis and this is the first step towards the goal of identifying novel therapeutic targets in the leukaemia microenvironment. To perform the project, the student will develop expertise in

• Animal handling and tissue preparation;

• Tissue culture;

• Immunohistochemistry;

• Flow cytometry and cell sorting;

• Gene expression analysis References: Laurence Cheung, Jennifer Tickner…Charles Mullighan, Rishi Kotecha, Ursula Kees. New therapeutic opportunities from dissecting the pre-B leukemia bone marrow microenvironment. Leukemia 2018;32 (11):2326-38 Kotecha RS, Cheung LC. Targeting the bone marrow microenvironment: a novel therapeutic strategy for pre-B acute lymphoblastic leukemia. Oncotarget. 2019;10(19):1756-7.


• BSc (Hons)

• Good oral and written communication skills Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project

☐ Full scholarship offered by project For more information, please contact: Dr Laurence Cheung (08) 6319 1345 [email protected]

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Identification of Novel Drug Combinations to Cure High-Risk Infant Leukaemia Research Program Cancer Research Group Leukaemia and Cancer Genetics Start Date February 2020 Chief Supervisors Dr Laurence Cheung (Telethon Kids Institute, Curtin University)

Dr Rishi Kotecha (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors TBC Project Outline Leukaemia is the most common type of cancer in children, and most patients have a

disease called acute lymphoblastic leukaemia or ALL. Improvement in therapy over the past 50 years has seen a dramatic increase in the survival rate of children with ALL, and modern therapies for children achieve cure rates in more than 90% of patients. This is in sharp contrast to infants, who are defined as being less than one year old at the time they are diagnosed. For those with a particular genetic aberration, called MLLr, in their leukaemia and less than 3 months of age at diagnosis, outcome is dismal with 5-year survival of less than 40% and 16% respectively. Patients are treated with up to twelve potent chemotherapeutic drugs, yet more intensified therapy does not improve outcome for these babies due to an increase in toxic deaths, as demonstrated in international trials. Novel therapies are desperately needed. We have established a preclinical drug testing pipeline aiming to discover novel drugs to treat infant with ALL. This project will involve high-throughput in vitro drug efficacy assessment as well as evaluation of the drug combination therapy using xenograft models. To perform the project, the student will develop expertise in

• Animal handling and tissue preparation;

• Tissue culture;

• In vitro drug testing assays;

• Flow cytometry;

• RNA and protein extraction References: 1. Mark Cruickshank, Jette Ford, Laurence Cheung…Rishi Kotecha, Ursula Kees. Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin. Leukemia. 2017;31(1):40-50. 2. Laurence Cheung, Mark Cruickshank…Richard Lock, Ursula Kees, Rishi Kotecha. Romidepsin enhances the efficacy of cytarabine in vivo, revealing histone deacetylase inhibition as a promising therapeutic strategy for KMT2A-rearranged infant acute lymphoblastic leukemia. Haematologica 2019


• BSc (Hons)

• Good oral and written communication skills Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project

☐ Full scholarship offered by project For more information, please contact: Dr Laurence Cheung (08) 6319 1345 [email protected]

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Impact of Copy Number Amplifications in Paediatric Acute Leukaemia Research Program Cancer

Research Group Leukaemia and Cancer Genetics Start Date March 2020 Chief Supervisor Dr Sébastien Malinge (Telethon Kids Institute, The University of Western Australia) Other Supervisors - Project Outline Leukaemia is the most common type of cancer in children. Remarkable therapeutic

advances have been made over the past sixty years, but specific types of acute leukaemia still have a poor prognosis and today, death from leukaemia still accounts for 22% of all cancer-related deaths for children in Australia. Current therapeutic approaches have now reached their maximum potential, highlighting the need for new efficacious treatments. Copy number amplifications of whole chromosomes or specific regions of the genome are a hallmark of cancer, but their role in tumour development remains mostly unknown. In paediatric leukaemia, gains of chromosome 21 is the most common alterations occurring in up to 40% of cases acute megakaryoblastic leukaemia (AMKL) and in B-cell leukaemia (B-ALL) and but very rarely seen in T cell leukaemia (T-ALL). Strikingly, children with Down syndrome (constitutive trisomy 21) have increased risk of developing B-ALL and AMKL, and have a decreased incidence of T-ALL compared to other children. In this project, we aim to develop new in vitro and in vivo models to better understand the role in leukaemia development and prevention. These models will represent useful tools to 1- identify causative chromosome 21 genes affected by copy number amplifications, and 2- provide models to test new pharmacological agents. Over the course of this project, the student will develop expertise in:

• Next generation sequencing (WES/WGS, RNAseq),

• Flow cytometry and cell sorting,

• Animal handling, tissue preparation and drug testing,

• Tissue culture and molecular biology,

• CRISPR/Cas9 technology and screening strategies. This project represents a proof of concept study showing that targeting copy number amplification is a new era of investigation to develop alternative therapeutical strategies and improve outcome of these children.

Suitable For ☒ Honours ☐ MD ☒ Masters ☐ PhD Essential Skills & Qualifications

• BSc (Hons)

• Good oral and written communication skills Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Sébastien Malinge (08) 6319 1351 [email protected]

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Aggressive Brain Cancer: Determining the Role of ErbB4 Research Program Cancer Research Group Oncogenic Signalling Laboratory Start Date February 2020 Chief Supervisor Professor Terrance Johns (Telethon Kids Institute) Other Supervisors Dr Naomi Alexander (Telethon Kids Institute) Project Outline Glioblastoma Multiforme (GBM) is the most common and aggressive form of primary

brain cancer affecting adults. A paediatric counterpart, Diffuse Intrinsic Pontine Glioma (DIPG), is equally aggressive and accounts for 10% of childhood brain cancers diagnosed every year in Australia. GBM’s are diffuse and highly invasive, and patients usually die within two years of diagnosis. Despite decades of research, treatments for these cancers are less than optimal, as surgery is usually not curative, and chemotherapy and radiotherapy only provide modest benefit. Consequently, survival rates for these cancers have remained relatively static over the past 30 years. Therefore, discovering new therapeutic approaches is a crucial step towards developing more effective treatments that extend patient’s lives. ErbB4 is a member of a protein family collectively known as the ‘Epidermal Growth Factor Receptors’ (EGFR), which comprises EGFR, ErbB2, ErbB3 and ErbB4. These proteins are anchored at the cell surface and act as transducers, receiving signals from the extracellular environment, and passing these signals on to other proteins within the cell. This leads to cellular responses to the original signal, that affect survival, growth and movement. In cancer cells, it is known that such signalling pathways can become deregulated, and in GBM, around 50% of patients show increased levels of EGFR. Hence, many new therapeutics have been directed towards EGFR but have not been effective. Analyses of GBM samples have indicated that ErbB4 is the second most prominent member in GBM, and at the protein level, higher amounts of ErbB4 have been found in both GBM and DIPG cells, compared to normal cells. Relatively high amounts of ErbB4 have also been detected in childhood brain cancers such as medulloblastoma and ependymoma. We are interested in understanding the role of ErbB4 in GBM and DIPG, including the expression levels and signalling activity of this protein. Our lab has generated patient derived GBM cell lines, several of which show high expression levels of ErbB4. We aim to ‘knock down’ this protein in our GBM cells using modern molecular biology techniques (CRISPR) and compare the features of these cells to those that have high amounts of ErbB4. This project will primarily use techniques in cell and molecular biology, including tissue culture, Western blotting, immunoprecipitation, single cell Western blotting, cell staining, morphology and proliferation assays.

Suitable For ☒ Honours ☐ MD ☐ Masters ☒ PhD Essential Skills & Qualifications

• A relevant undergraduate degree

Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☒ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Professor Terrance Johns (08) 6319 1353 or 0402 490 131 [email protected]

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Repurposing Ion Channel Drugs to Sensitize Diffuse Intrinsic Pontine Glioma to Targeted Therapies Research Program Cancer Research Group Oncogenic Signalling Laboratory Start Date February 2020 Chief Supervisor Professor Terrance Johns (Telethon Kids Institute) Other Supervisors Dr Panimaya Jeffreena Miranda (Telethon Kids Institute) Project Outline Diffused Intrinsic Pontine Glioma (DIPG) is a fatal type of brain cancer that affects

children. It accounts for nearly 10% of all childhood brain cancers diagnosed in Australia every year. DIPG is very hard to treat, with no effective treatment at hand. Surgery is too risky, as DIPG diffuses through the brain stem and infiltrates through the surrounding regions. In addition, chemotherapy is ineffective, and radiotherapy provides only temporary relief of symptoms, extending survival by just 3 months. An alternative and promising approach is targeted therapy, a treatment that uses drugs targeting specific proteins directly involved in carcinogenesis to prevent cancer cell growth and progression. This approach has proven effective against different types of cancers. However, targeted therapy has been ineffective against DIPG, as cancer cells develop resistance following treatment. A key factor that might be driving this resistance is neuro-plasticity. Plasticity is an inherent property of brain cells that allows them to adapt to different conditions in their environment. DIPG cancer cells originate from neural cells and use their innate plasticity to evade targeted therapy. A key player in neuroplasticity are ion channels, pore-forming proteins present on the cell membrane, where they regulate the flow of small charged molecules, such as sodium and potassium, in and out of the cell. Changes in the flow of ions across the cell membrane can lead to changes in the internal wiring of the cell, allowing them to be critical mediators of neuro-plasticity by rewiring cellular signalling. However, no study has assessed the anti-cancer efficacy of clinically approved ion channel drugs that modulate cellular plasticity in combination with targeted therapies. In this project, we will explore the efficacy of a novel combination therapy using clinically approved ion channel drugs and targeted therapies. We will focus this novel therapeutic approach on patient-derived DIPG cell lines and in orthotopic mouse xenograft models of DIPG. This approach will help us understand the mechanism of action of our combination therapy and the role of ion channels in re-sensitizing DIPG cells to targeted therapy. Findings from this study hold great potential to be translated into clinical trials for paediatric DIPG. Ultimately, the outcome of this project is expected to identify improved combination therapies that will increase survival rates of DIPG patients.


• A relevant undergraduate degree



15

Understanding the Function of Ion Channels in High Grade Glioma Research Program Cancer Research Group Oncogenic Signalling Laboratory Start Date March 2020 Chief Supervisor Professor Terrance Johns (Telethon Kids Institute) Other Supervisors Dr Emily Fletcher (Telethon Kids Institute) Project Outline Why are successful targeted therapies available for many types of cancer but not for the

deadliest of brain cancers: high-grade glioma (HGG)? Targeted therapeutics have been developed for HGG but have failed. One possible reason for this failure may involve cellular plasticity: the ability of cells to adapt to changes in their environment by re-wiring their inner functions and finding new pathways to survive. HGG cells are, essentially, neural cells and may be using their innate plasticity to evade the effects of targeted drugs. This plasticity is largely driven by a special type of trans-membrane proteins called ion channels. Ion channels are pore-forming proteins found in the cell’s membrane, which allow electrically charged metal ions to pass in and out of the cell. Ion channels have been shown to be critical mediators of cell plasticity. However, nothing is known about the role of ion channels in neuroplasticity associated with adaptive drug resistance. Targeting ion channels in HGG cells with clinically approved drugs may be a fast and effective way to overcome HGG plasticity and increase the anti-tumour activity of targeted therapies. Using HGG cell lines, our laboratory is studying mutations and expression patterns in ion channel genes, which could be mediating HGG plasticity. We are also exploring ways to target these aberrations with targeted therapies. This is achieved through:

1. Genome- and transcriptome-sequencing analysis of public patient data; 2. Generating in-vitro and in-vivo models for testing novel therapies; and 3. Testing the functional impact of these alterations.

The project is designed to elucidate the role of ion channel alterations in HGG plasticity, with the goal of identifying potential therapeutic targets. The student will be part of the Oncogenic Signalling Lab, performing RNA and protein studies. The student will develop expertise in:

• Molecular biology;

• Tissue culture;

• RNA and protein extraction;

• Q-PCR and western blotting; and

• Immunohistochemistry.


• Undergraduate degree in molecular biology



16

Exploring how Ongoing Exposure to Low Dose Ultraviolet Radiation Prevents Weight Gain and Suppresses the Development of Type-2 Diabetes Research Program Diabetes and Obesity Research Group Cardiometabolic Sunhealth Start Date July 2019 Chief Supervisor Dr Shelley Gorman (Telethon Kids Institute, The University of Western Australia) Other Supervisors Dr Vance Matthews (UWA School of Medicine and Pharmacology) Project Outline Skin exposure to the ultraviolet radiation (UVR) component of sunlight results in the

production of biological mediators, like vitamin D and nitric oxide that can modulate disease development. Our novel studies have shown that chronic skin exposure to low dose UVR suppressed weight gain and signs of type-2 diabetes in adult mice fed a high fat diet through a nitric oxide-dependent mechanism. In this project, we will use our animal modelling approach to explore mechanisms by which ongoing exposure to low dose (and safe) UVR curbs weight gain and the development of type-2 diabetes in mice fed a high fat diet. These mechanisms may include examining the effects of UVR on: Metabolic processes and circadian rhythm in brown adipose tissue; Regulating appetite and/or activity; and IL-6-dependent processes that affect metabolism. These studies may have important ramifications for the development of health policies and therapies that consider both the beneficial and detrimental effects of ongoing exposure to sunlight in early life and beyond. Please note: the availability of this project is dependent on the research team obtaining further funding.


• Undergraduate degree in Bachelor of (Medical) Science or related degree

• (with 1st-class or very good 2nd-class Honours for PhD)

• Excellent written and oral communication skills

• Very good organisational skills, motivation and dedication

• Some statistical knowledge Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☒ Top-up scholarship offered by project

☐ Full scholarship offered by project For more information, please contact: Dr Shelley Gorman (08) 6319 1747 or 0409 114 452 [email protected]

17

Testing the Capacity of an Online Tool to Promote Safe Sun Behaviours in Teenagers Research Program Diabetes and Obesity Research Group Cardiometabolic Sunhealth Start Date July 2019 Chief Supervisor Dr Shelley Gorman (Telethon Kids Institute, The University of Western Australia) Other Supervisors TBC Project Outline In this project, we will test a prototype online tool that has recently been developed, with

the goal of helping adolescents better balance their health needs for sun protection and sun exposure. Sun protection is important for this age group, as intermittent excessive exposure (causing sunburn) in childhood and adolescence is a major risk factor for melanoma, and other skin cancers. Melanoma is the most common cancer of young adults in Australia (15-29 year olds). Recent research in WA youth has identified that sun protection messages need to target adolescents who are less likely to engage in the most effective sun protection behaviours, and are at increased risk of sunburn. Some safe sun exposure is necessary for health benefits, such as vitamin D. However, it is not easy to frame health messages that provide sun safety for protection from sunburn but allow sufficient sun exposure for optimal vitamin D. To our knowledge there is no online tool or App that specifically promotes better sun health behaviours, which has also been shown to subsequently improve sun behaviours by adolescents. Summary. In this project, we will test a newly developed online tool, designed for and with adolescents, on its capacity to actively engage the target audience in an entertaining and age-appropriate way to deliver rigorously vetted health information around optimal sun protection and exposure. Project aim. To develop and pilot test a prototype online tool that aims to improve the knowledge and behaviours that young adolescents have around safe sun protection and exposure practices for vitamin D. Research objective. Obtain end-user responses (‘process’, including; engagement, functionality, aesthetics and information quality) and pilot test the capacity of the developed online tool to improve the sunhealth knowledge and behaviours in an independent cohort of young adolescents (aged 12-13).

Suitable For ☒ Honours ☒ MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Undergraduate degree in Bachelor of (Medical) Science or related degree

• Excellent 2A Honours (if PhD)

• Statistical skills


• Very good organisation

• Motivation and dedication Ethics Approval ☐ Obtained ☒ Not Obtained (in development) Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Shelley Gorman (08) 6319 1747 or 0409 114 452 [email protected]

18

Co-Developing and Trialling an Intervention to Help Teachers and Coaches Support Children and Adolescents with Type 1 Diabetes when Physically Active Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisor Dr Leanne Fried (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital)

Dr Vinutha Shetty (Telethon Kids Institute, Perth Children’s Hospital) Project Outline The physical and psychological benefits of physical activity are well recognized for people

with type 1 diabetes (T1D). However, the challenges associated with managing T1D while physically active can be a barrier to a physically active lifestyle. A recent research project conducted through the Children’s Diabetes Research Centre found that a significant challenge experienced by adolescents when physically active was dealing with a lack of knowledge of T1D of teachers at school and coaches in the community. This not only meant that they didn't receive the support they needed to be physically active but ‘wrong’ knowledge and lack of trust caused frustration and stress. This project involves using adolescents and young adults with T1D as co-researchers to develop and trial an intervention that will enable teachers and coaches to support children and adolescents with T1D when physically active. The specific aims of the project are:

• To co-develop an intervention that will support children and adolescents with T1D when physically active at school and in the community (targeted at teachers and coaches)

• To document the co-design process

• To trial the intervention and determine its feasibility and acceptability. The project can be conducted as a qualitative study using a Participatory Action and Reflection methodology. Workshops will enable intervention co-design to occur and data can be collected using field notes, video recording and tasks. Appropriate analysis will be a qualitative content analysis approach. The project will be conducted through the Children’s Diabetes Centre with support from the Health Promotion and Education Research group at Telethon Kids.


• Undergraduate degree in psychology, health science, education or related degree

• Excellent communication skills Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Leanne Fried (08) 6319 1480 [email protected]

19

Developing and Trialling a Peer Support Program for Students with Type 1 Diabetes in Schools

Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date No fixed start date Chief Supervisor Dr Leanne Fried (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors Professor Donna Cross (Telethon Kids Institute)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Adolescents with diabetes can experience physical, emotional, and social stress due to the

demands of a complicated medical regimen. These demands can sometimes result in non-compliance. As adolescents decrease their dependence on their parents, they often rely on peers for support. Although at times peers may be negative influences they can also be important sources of constructive support. For example, peers are more likely than family members to provide companionship and emotional support in relation to diabetes care. A recent study found that more general positive relations with peers at one point in time predicted less diabetes distress a year later. This project involves developing a group-based peer support program for adolescents with T1D and trialing this program in a school. The peer-support program will be developed with the help of adolescents with T1D. The specific aims of the project are:

• To develop a group-based peer-support program for adolescents with T1D and;

• To determine the effects of this program on the adolescent’s diabetes management, diabetes distress and social functioning.

The project will be conducted as a mixed methods study. Quantitative data will measure the effects of the intervention on diabetes management and social functioning while qualitative data will help to shape the intervention and determine its feasibility and adaptability. The project will be conducted through the Children’s Diabetes Centre with support from the Health Promotion and Education Research Group. The two main phases of this project: developing and trialling the intervention could be suitable as separate student projects.



• Excellent communication skills Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project

☐ Full scholarship offered by project For more information, please contact: Dr Leanne Fried (08) 6319 1480 [email protected]

20

Developing Educational Resources for Sports Coaches and Teachers to Support Children and Adolescents with Type 1 Diabetes be Physically Active Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisor Dr Leanne Fried (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors Professor Donna Cross (Telethon Kids Institute)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Along with insulin and diet, exercise has been recognised as one of the three essential

components of managing type 1 diabetes (T1D). However, the challenges associated with managing T1D while physically active can be a barrier to a physically active lifestyle. A research project conducted through the Children’s Diabetes Research Centre found that a significant challenge experienced by adolescents when physically active was dealing with a lack of knowledge of T1D of teachers at school and coaches in the community. This not only meant that they didn't receive the support they needed to be physically active but ‘wrong’ knowledge and lack of trust caused frustration and stress. The aim of this project is to develop resources to assist sports coaches and teachers to support young people with type 1 diabetes to engage in physical activity, through 4 stage process.

• Determine what resources/training is currently available and assess gaps in knowledge

• Run workshops with peak sporting bodies, sports coaches and teachers to determine needs and resource format

• Co-develop resources as determined by workshops e.g. short online learning training modules, handouts, website with young people with type 1 diabetes and participants from stage 2

• Dissemination of resources The project will be conducted through the Children’s Diabetes Centre with support from the Health Promotion and Education Research Team at Telethon Kids.


• Undergraduate degree in Psychology, Health Science, Education, Health Promotion or related degree


☐ Full scholarship offered by project group For more information, please contact: Tanyana Jackiewicz (08) 6456 4616 [email protected]

21

Effect of High Blood Glucose Levels on Executive Function, Attention and Driving Performance on a Driving Simulator in People with Type 1 Diabetes Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date July 2019 or July/February 2020 Chief Supervisor Professor Paul Fournier (UWA School of Human Sciences) Other Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline It is well established that several years of exposure to high blood glucose levels in people

with type 1 diabetes mellitus (T1D) can be detrimental to the central and peripheral nervous systems. In particular, reaction time, cognitive function (e.g. executive function and attention), and driving performance have been reported to be adversely affected by T1D. What is still unclear, however, is the impact that an acute increase in blood glucose levels (e.g. after a meal) may have on driving performance and cognitive function. Although a small number of studies have investigated the effects of acute hyperglycaemia on cognition, some cognitive abilities essential to everyday tasks, such as driving, have not been thoroughly assessed; namely, executive functions, attention, and driving ability. For these reasons, the primary aim of this proposed project is to test the hypothesis, in people with T1D, that an acute exposure to high blood glucose levels will impair their driving performance in a driving simulator. We also hypothesise that both attention and executive function will be impaired upon exposure to acute hyperglycaemia.


• Initiative and dedication

• High level of written communication skills

• High level of organisation and time management skills

• Ability to complete projects on time

• Willingness to learn new skills

• Excellent ability to work independently and as part of a team

• Good interpersonal skills

• Good communication skills Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☒ Top-up scholarship offered by project group for Honours/Masters projects

☒ Full scholarship offered by project group for Honours/Masters projects For more information, please contact: Tanyana Jackiewicz (08) 6456 4616 [email protected]

22

Effect of Swimming and Head-Out Water Immersion in Cold Water on the Risk of Hypoglycaemia in Type 1 Diabetes Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date July 2019 or July/February 2020 Chief Supervisor Professor Paul Fournier (UWA School of Human Sciences) Other Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Physical activity increases the risk of hypoglycaemia in individuals with type 1 diabetes

(T1D), with the associated increased fear of hypoglycaemia contributing to their lower participation rates in regular exercise and lower than average fitness levels. For this reason, a number of recommendations have been published to reduce such risks of hypoglycaemia. Unfortunately, one major limitation with these recommendations is that they generally overlook the impact that some environmental conditions may have on blood glucose response to exercise. Since cold water immersion increases glucose oxidation rate and may inhibit the production of glucose by the liver, this raises the issue of whether upright immersion or swimming in cold water increases hypoglycaemia risk in people with T1D. This is a clinically important issue given the increased risk of drowning associated with hypoglycaemia. Since this issue has not been investigated before, the primary aims of this proposed research project are to test the hypotheses that (a) head out of water immersion in cold (20oC) compared to thermoneutral water (32oC) is associated with a faster rate of fall in blood glucose level; and (b) exercising in cold water causes a greater rate of fall in blood glucose level compared to exercising under thermoneutral conditions.











23

Effect of Hypoxia Typical of High Altitude on the Accuracy of Continuous Glucose Monitors and its Impact on Blood Glucose Management in Individuals with Type 1 Diabetes Mellitus Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date July 2019 or July/February 2020 Chief Supervisor Professor Paul Fournier (School of Human Sciences, University of Western Australia) Other Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Regular self-monitoring of blood glucose levels using continuous glucose monitors (CGM)

provides an effective means to minimise both hypoglycaemia risk and the magnitude of the glycaemic excursions experienced by people with type 1 diabetes. One potential limitation with this technology relates to the glucose sensors they use to measure glucose levels as some of these sensors maybe affected by the levels of ambient oxygen. Indeed, meters that use a glucose oxidase-based enzyme reaction may misread glucose levels under conditions of low blood oxygen tension. Although this may have been a limitation with the first generation of glucose-oxidase-based sensors because their electrochemical detection of glucose was dependent on ambient oxygen levels, current CGMs rely on oxygen-independent glucose-oxidase-based sensors, thus implying that these devices may not be affected by ambient oxygen levels. Whether this is the case remains to be determined. This is an important clinical issue to address given the popularity of high-altitude destinations and activities (e.g. trekking, skiing) associated with low oxygen levels. Our primary aim is to examine the extent to which the accuracy of current CGMs is affected by the hypoxic conditions found at high altitude and thus evaluate whether these devices provide reliable blood glucose management tools for individuals with type 1 diabetes.











24

How Does Mode of Delivery Influence Risk of Childhood Type 1 Diabetes in Western Australia? Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisor Dr Aveni Haynes (Telethon Kids Institute) Other Supervisors Mr Grant Smith (Telethon Kids Institute)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Childhood type 1 diabetes (T1D), thought to be the result of environmental and genetic

factors, continues to increase in Western Australia (WA) but the cause of this increase unknown. Birth by Caesarean-section delivery has been shown to increase the risk of childhood T1D by 20%, but the mechanism for this association remains unclear. Technological and methodological advances in the burgeoning area of microbiome research have provided evidence that mode of delivery is a significant modifier of the infant gut microbiome, and importantly, that the infant gut microbiome has an important influence on early immune system development and maturation. Therefore, there is now a biologically plausible mechanism via which birth by Caesarean section may influence risk of later onset T1D. In WA, >99% of children diagnosed with T1D <15 years of age are managed by the diabetes team at Perth Children’s Hospital (PCH) and their data are stored in the Western Australian Children’s Diabetes Database (WACDD). In addition, data are available on all births in WA from the Midwives’ Notification System (MNS), a statutory data collection maintained by the Department of Health. This project aims to better define the relationship between mode of delivery and risk of childhood T1D using a case-control study design and data linkage. Cases will be identified from the WACDD and defined as all children with T1D diagnosed <15 years, born in WA between 1995 and 2017. Perinatal variables to be analysed will include e.g. gestational age, infant birth weight, maternal age, parity, maternal pre-existing diabetes, complications of pregnancy and labour, labour onset and mode of delivery.

Suitable For ☐ Honours ☐ MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Use of SPSS/STATA/R or other statistical package


☒ Full scholarship offered by project group For more information, please contact: Tanyana Jackiewicz (08) 6456 4616 [email protected]

25

How is Maternal Vitamin D Sufficiency During Pregnancy Associated with the Risk of Islet Autoimmunity Development in Children at Risk of Type 1 Diabetes? Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date March 2020 Chief Supervisor Dr Aveni Haynes (Telethon Kids Institute) Other Supervisors Mr Grant Smith (Telethon Kids Institute)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Early environmental determinants of pancreatic islet autoimmunity: a pregnancy to early

life cohort study (ENDIA) in children at risk of type 1 diabetes (T1D) is a multi-centre study involving researchers in South Australia, Victoria, New South Wales, Western Australia and Queensland. (www.endia.org.au). Over 1,300 pregnant women who have T1D or where their unborn child has a first degree relative with T1D have been recruited to the study and the children are being followed up from birth to 10 years of age. There are numerous observational epidemiological studies reporting an association between low Vitamin D levels with increased risk of childhood T1D. ENDIA has the unique opportunity to further examine the influence of vitamin D levels on the development of islet autoimmunity by analysing the association between prenatal vitamin D levels and modifiable environmental factors such as dietary intake during pregnancy and infancy, compliance with supplementation or treatment if vitamin D deficiency is diagnosed, and the risk of islet autoimmunity in children at risk of T1D. This study aims to:

• Determine the prevalence of vitamin D deficiency during pregnancy in the ENDIA study cohort

• Investigate the association between vitamin D deficiency and antecedent factors being evaluated in the ENDIA study cohort

• Investigate the association between vitamin D deficiency during pregnancy and the development of persistent islet autoimmunity in the ENDIA study cohort


Outstanding undergraduate in Health Science, Public Health Use of SPSS/STATA/R or other statistical package Good communication and organisational skills


☒ Full scholarship offered by project group For more information, please contact: Tanyana Jackiewicz (08) 6456 4616 [email protected]

http://www.endia.org.au/

26

Impact of Food on Glycaemic Control in Individuals with Type 1 Diabetes Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors - Project Outline The Children’s Diabetes Centre is an integrated clinical and research centre conducting

research into Type 1 diabetes (T1DM) and childhood onset Type 2 diabetes. The Children’s Diabetes Centre includes researchers at the Telethon Kids Institute’s Diabetes Research Team and researchers and clinicians within the Diabetes Service at Perth Children’s Hospital as part of the Western Australian Department of Health. Type 1 Diabetes is a 24/7 disease that requires constant management and vigilance. Blood glucose is affected by every mouthful of food and exercise — even sleeping, stress, fatigue, puberty, time of the day, time of the year, illness and temperature can affect blood glucose levels. The goal of the Children’s Diabetes Centre is to improve the lives of children, adolescents and young adults living with diabetes and their families by improving outcomes, both now and into the future. Our primary objective is to generate significant new knowledge that will lead to tangible improvements in care. We do this by focused research studies across 6 research themes including food and nutrition and our research involves clinical investigations, clinical trials, epidemiological studies and qualitative research projects and we translate the results of these studies into the clinic and the community. Our food and nutrition theme aims to better understand the impact of food on glycaemic control – that will be progressively translated into clinical practice and guidelines. Specific studies are dependent on the interest of the prospective student. The Centre offers PhD and Honours scholarships to competitive students.


• Outstanding academic record in relevant discipline

• First class honours in a relevant discipline

• Interest in clinical dietetics/nutrition

• Good communication skills Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☒ Top-up scholarship offered by project group

☒ Full scholarship could be available to outstanding student For more information, please contact: Tanyana Jackiewicz (08) 6456 4616 [email protected]

27

Is the Recommendation to Decrease Basal Insulin Dose Pre-Exercise Conducive to Severe Hyperglycaemia During and After Exercise? Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date July 2019 or July/February 2020 Chief Supervisor Professor Paul Fournier (UWA School of Human Sciences) Other Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Current guidelines recommend that people with type 1 diabetes (T1D) should reduce

their basal insulin dose by 25-50% prior to exercise to minimise their risks of hypoglycaemia both during and after exercise. However, these recommendations are challenged by our recent findings that when exercise is performed under basal insulin conditions, with no prior insulin dose adjustments, blood glucose levels remain stable or change little. These findings suggest that reducing basal insulin levels prior to a bout of high intensity exercise might be conducive to a marked increase in blood glucose levels, and thus be detrimental to blood glucose management. For this reason, our aim is to test the hypothesis that the recommendation to reduce basal insulin dose by 25 or 50% prior to engaging in a bout of high intensity exercise is conducive to a high increase in blood glucose levels in people with T1D.









• Good communication skills Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☒ Top-up scholarship offered by project group for Honours/Masters projects


28

Managing Type 1 Diabetes during Exercise – A Descriptive Study of Competitive Athletes with Type 1 Diabetes Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisors Professor Tim Jones (Telethon Kids Institute, Perth Children’s Hospital)

Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors - Project Outline Type 1 Diabetes Mellitus (T1DM) is a chronic auto-immune disease affecting the

pancreas’s insulin production, causing high-blood sugar levels (hyper-glycaemia). Its primary age of onset is in childhood and adolescence. The primary intervention for T1DM is insulin therapy, strongly supported by healthy diet and regular exercise and physical activity (P-A). The benefits of P-A and exercise for all people are extensive, and is associated with greater cardiovascular health, muscle and bone strength, improved mood and self-esteem, and reducing the risk of cardiovascular disease, depression, osteoporosis and other chronic diseases. This is particularly relevant to individuals with T1DM, as disease complications are associated with poorer diabetic control and management. Although exercise is a mainstay of T1DM management, children and, in particular adolescents, with T1DM have been shown to spend less time being physically active than their non-diabetic peers. This is often due to difficulties faced in managing their condition including:

• Variability of blood glucose levels before, after and during exercise

• Planning and consumption of appropriate foods

• Practical difficulties associated with the testing of blood glucose levels

• Utilising new technologies in diabetes care

• Understanding social or community perceptions about exercising with T1DM, as well as managing their own self-confidence.

Historically, athletes with T1DM are highly proficient at managing their condition independently and are their own ‘expert’ or ‘physician’. Therefore, clinicians can often learn valuable lessons from this patient cohort. The aim of this study to describe the strategies used by young (13-30 years of age) competitive athletes with T1DM to manage their condition while performing. This information will be used to inform in clinic and community interventions to improve physical activity rates in young people with T1DM. This survey research project will collect information from young (13-30 years of age) competitive athletes with T1DM across a variety of sports and athletic pursuits. This descriptive study is also expected to reveal areas of future research regarding T1DM and physical activity.

Suitable For ☒ Honours ☐ MD ☐ Masters ☐ PhD Essential Skills & Qualifications

• Undergraduate in health sciences, public health, exercise science or other relevant area

• Interest in survey and qualitative research

• Good communication skills Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project group


29

Negotiating the Path to Self-Management of T1D – Adolescents’ and Parents’ Perspectives Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisor Dr Leanne Fried (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital)

Dr Keely Bebbington (Telethon Kids Institute) Project Outline Many adolescents with type 1 diabetes (T1D) and their parents struggle through the

adolescent period with sharing of responsibility for diabetes management and movement towards adolescent self-management. Research has shown that these struggles can result in poor blood glucose control for the adolescent with T1D and raised levels of anxiety for both the adolescent and the parent. To help adolescents with type 1 diabetes and their parents through this transition it is useful to better understand how the transfer of responsibility is negotiated, what conflicts can occur during this period and what works to help the adolescent, parents and family as a whole. This study will aim therefore to better understand the transition to self-management from the perspectives of both the adolescent with T1D and their parents. This project will be conducted as a mixed method study. Quantitative data will be collected to measure self-management, quality of life and child-parent conflicts while qualitative data will be used to explore in depth how adolescents and parents negotiate this transition and what they need to help with this. This study will be conducted through the Children’s Diabetes Centre with support from the Health Promotion and Education Research group at Telethon Kids Institute. As a student project, the student will be involved in all aspects of this project including conceptualisation, data collection, data analysis and translation.




☐ Full scholarship offered by project group For more information, please contact: Dr Leanne Fried (08) 6319 1480 [email protected]

30

Using Continuous Glucose Monitoring and a Carbohydrate Algorithm to Manage Blood Glucose Levels during Exercise in Adolescents with Type 1 Diabetes Research Program Diabetes and Obesity Research Group Diabetes and Obesity Research Start Date January 2020 Chief Supervisor Professor Elizabeth Davis (Telethon Kids Institute, Perth Children’s Hospital) Other Supervisors Professor Paul Fournier (UWA School of Human Sciences) Project Outline Insert 1-2 short paragraphs in lay terms outlining project summary, aims/objectives,

research group, and student’s main responsibilities Physical exercise can cause both low and high blood glucose levels in children and adolescents with type 1 diabetes mellitus. Due to the immediate and potentially serious consequences of untreated low blood glucose levels, it is often being regarded as the main barrier to a physically active lifestyle. In recent years, there has been an increase in the use of real-time continuous glucose monitoring (rtCGM) technology to better manage glucose levels. However, studies have not yet demonstrated the optimal use of rtCGM to reduce the time spent with low and high blood glucose levels during physical activity. The aim of this study is to trial a carbohydrate algorithm based on rtCGM readings during 60 minutes of moderate intensity cycling, in 14-16 year old adolescents with T1DM. Participants will complete a familiarisation visit with a VO2 peak test followed by two testing sessions. One session will use the carbohydrate algorithm based on the rtCGM and the other will give carbohydrates based on the standard guidelines. The Centre offers Honours scholarships to competitive students.


• Undergraduate in Health Sciences, Public Health, Exercise Science or other relevant area

• Good communication skills Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group


31

Rapid Diagnosis of Rare Genetic Diseases in Paediatric Patients Research Program Genetics and Rare Diseases Research Group Genetic and Health Start Date Honours: February 2020

PhD: February 2020 onwards Chief Supervisors Dr Vanessa Fear (Telethon Kids Institute)

Dr Genevieve Syn (Telethon Kids Institute) Other Supervisors - Project Outline Rare diseases collectively affect more than 190,000 Western Australians, including 63,000

paediatric patients, and accordingly have been identified as a public health priority. Around 80% of all rare diseases have a genetic basis. The advent of Next Generation Sequencing has allowed high speed, affordable sequencing, with Whole Exome Sequencing (WES) now implemented in WA as the diagnostic method of choice for rare diseases. However, diagnosing a child with a rare disease requires that the genetic variant has previously been functionally characterised, validated and reported. This means that many children with rare diseases present with previously unseen single nucleotide variants (SNVs) that are of uncertain significance. Even in cases where the new mutation is localised to a region known to be important to gene function, providing the patient with a diagnosis requires validation of the effects of the new variant. This means that many patients and their families endure months or even years of not knowing the cause and best treatment for their disease, with the psychological burden this entails. CRIPSR technology provides a new way to rapidly validate the effects of rare variants found in patients. This project will use CRISPR homology directed repair, with click chemistry, and CRISPR base editing to mutate human inducible pluripotent stem cells (iPSCs) with the SNV of interest. The impact of these SNVs on relevant mesoderm, endoderm, ectoderm differentiation pathways in iPSCs will then be investigated using RNAseq, flow cytometry and protein analysis. This project will contribute to our genetic and rare disease studies that aim to reduce the time to paediatric patient diagnosis. This is highly valuable as an early, accurate diagnosis may alleviate disease progression, reduce complications and co-morbidities, and improve patient quality of life.


• Undergraduate degree in Biochemistry, Molecular Biology, or similar

• Excellent communication and writing skills For PhD candidates:

• Minimum 2A honours degree Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Vanessa Fear (08) 6319 1022 [email protected]

32

Automated Analysis of Clinical Lung Samples through Machine Learning Research Program Respiratory Health Research Group Airway Epithelial Research Start Date February 2020 Chief Supervisor Dr Luke Garratt (Telethon Kids Institute, The University of Western Australia) Other Supervisors Professor Jodie Simpson (The University of Newcastle)

Sarada Lee (Perth Machine Learning Group) Dr Tim Rosenow (Telethon Kids Institute) Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

Project Outline Chronic respiratory diseases are a major healthcare burden in Australia, either due to their high prevalence (asthma) or high severity (cystic fibrosis). To manage chronic respiratory diseases, infection and inflammation of the lung is typically interrogated by either collection of expectorated sputum or, in younger children or people who are not producing sputum, performing a wash of the lungs known as bronchoalveolar lavage. These clinical lung specimens are used to culture for infectious organisms and describe the immune cell burden in the airway. The latter is done by depositing cells on a glass slide and counting immune cell subsets after specialised stains. This project aims to develop a robust, automated analytical tool for identifying immune cell subsets in cytospins of clinical lung specimens. This will be done using machine learning approaches for image classification. The first part of the project will be to acquire high quality images of cytospins from asthma and cystic fibrosis clinical lung specimens, then annotating key features on the images including immune cells (i.e. neutrophils, eosinophils, lymphocytes, macrophages) and any distinct morphological features (necrosis, nuclei segmentation, Oil Red O positivity, mucous). The second part of the project will be to train the machine learning algorithms using learning and validation sets of images and then compare outcomes to prior manual analyses. The third part of the project will be to correlate outcomes from the automated analyses to clinical indicators such as symptoms, lung function and radiological assessments of disease. As automated image classification tools can be extremely informative and applied anywhere, tools successfully developed in this project could have applications in clinical care and/or clinical trials.


• Bachelor of Science or equivalent

• Above average written and oral communication skills

• Motivation and organisational skills

• Ability to work as part of a long-distance collaborative team Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Luke Garratt (08) 6319 1804 [email protected]

33

Establishing the Lung Virome Profiles in Cystic Fibrosis Children with and without Exacerbations Research Program Respiratory Health Research Group Airway Epithelial Research Start Date February 2019 Chief Supervisor Dr Patricia Agudelo-Romero (Telethon kids Institute) Other Supervisors Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

A/Professor Anthony Kicic (Telethon kids Institute, The University of Western Australia, Curtin University) Dr Luke Garratt (Telethon Kids Institute, The University of Western Australia) Dr Erika Sutanto (Telethon kids Institute) Dr Thomas Iosifidis (Telethon kids Institute)

Project Outline Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The lungs and digestive systems of individuals with CF function abnormally producing an excessive amount of thick and sticky mucus. Respiratory illnesses produced by viral infections could play a pivotal role in the decline of lung functions in CF patients, since the prevalence of these infections is higher in CF patients than in the normal population. Therefore, exploring the lung human virome is a key priority in order to evaluate the significance of this component of the lung microbiome in the progression of CF. Our main objective is to study the host-virome interaction in epithelial cells derived from CF children that have recorded exacerbation episodes, compared to those age-matched children who did not exacerbate. With this end, metatranscriptomics and metagenomics approaches will be performed for a whole virome detection, RNA and DNA viruses. Bioinformatic pipelines will be used to explore: (1) Viral population dynamics in CF and their implication during the exacerbations. (2) Variant calling analysis to detect mutations and polymorphisms from the known viruses. (3) De novo assembly to the identification of potential new viral species. Outcome from this study will give us to a better understanding about how the CF-associated lung environment influence in shaping the virome population.


• Above average written and oral communications skills.

• Motivation and organisational skills.

• Able to work as a part of a team. Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Patricia Agudelo-Romero (08) 9340 8140 [email protected]

34

Exploring the Therapeutic Potential of Phage Therapy to Treat Lung Infections in Children with Cystic Fibrosis Research Program Respiratory Health Research Group Airway Epithelial Research Start Date February 2020 Chief Supervisor A/Professor Anthony Kicic (Telethon kids Institute, The University of Western Australia,

Curtin University) Other Supervisors Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

Dr Luke Garratt (Telethon Kids Institute, The University of Western Australia) Dr Erika Sutanto (Telethon Kids Institute)

Project Outline Cystic fibrosis (CF) is a genetically inherited disease affecting mostly the Caucasian population. There are over 300 individuals with CF in WA and 12-15 newborns are diagnosed each year following newborn screening. As part of the Australian Respiratory Early Surveillance Team for CF, we have demonstrated that early lung damage present early in life and that the lungs of children with CF are prone to inflammation from birth. Cystic fibrosis is caused by mutations in the CFTR gene. Loss of its function leads to abnormal amounts of excessively thick and sticky mucus within the lungs which then traps bacteria. Recurrent infections of this kind over time leads to irreversible lung damage and death due to lung failure. Intravenous and inhaled antibiotic therapies remain the current treatment strategy for most lung infections. However, antibiotic resistant bacterial strains have emerged as major causes of mortality in hospitals worldwide and antibiotic resistance by various bacteria remains a serious problem in children with CF. This study will investigate the use of Bacteriophages (viruses that infect and kill bacteria, ‘phages’) as a novel therapeutic approach to treat freely available and biofilm causing infections. Being more specific and with less side effects, phage therapy is an exciting alternative that is much cheaper, less toxic, and more effective than current strategies.


• Bachelor of Science or equivalent.

• Above average written and oral communication skills;

• Motivation and organisational skills;

• Able to work as part of a team. Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: A/Professor Anthony Kicic (08) 6319 1799 [email protected]

35

Investigating the Role of Epithelial-Fibroblast Cross-Talk in Lung Fibrosis Research Program Respiratory Health Research Group Airway Epithelial Research Start Date February 2020 (also suitable for mid-year intake Hons) Chief Supervisor A/Professor Cecilia Prêle (Institute for Respiratory Health, The University of Western

Australia) Other Supervisors A/Professor Steven Mutsaers (Institute for Respiratory Health, The University of Western

Australia) A/Professor Anthony Kicic (Telethon Kids Institute, The University of Western Australia, Curtin University)

Project Outline The wide-ranging impact of fibrosis affects millions of people of all ages and has only limited and largely ineffective treatment options available for most sufferers. Current dogma suggests the development of fibrosis in the lung follows a similar pathway to normal wound healing, although there is chronic progression without resolution, suggesting the fine control of cellular functions that occur during wound healing is disturbed. Given the central role collagen deposition plays in fibrosis, drug development to date has focused on targeting fibroblasts and myofibroblasts to prevent excess matrix production and deposition. However, this approach has largely ignored what is becoming increasingly clear, that fibrosis results from abnormal communication between fibroblasts and epithelial cells.

In this study, we will use a co-culture system to examine TGF, Wnt and Jak/STAT-mediated responses contributing to extracellulara matrix protein deposition and regulation, cell proliferation, migration, as well as profibrotic cytokine and chemokine production in co-culture in vitro. The extent of epithelial cell migration, proliferation and apoptosis will be monitored using the IncuCYTE Zoom. The effect of epithelial apoptosis on extracellular matrix (ECM) deposition by fibroblasts will be assessed using the scar-in-a-jar (SIAJ) model of matrix deposition (a high throughput macromolecular crowding assay). Epithelial cells cultured on transwell inserts will be injured and transferred to fibroblast culture plates. The injury protocol will be optimised to determine if repeat, daily injury is required for accumulation of mediators and enhanced ECM deposition in the SIAJ model in vitro. Collagen I and IV, fibronectin, elastin and tenascin C deposition will be analysed at 48, 72 and 96 h post damage and quantified using Cell Insight CX7 high

content screening platform and by western blot. Cultures treated with 1 ng/ml TGF1 or

PDGF will be used a positive control. The extent of TGF, Wnt and Jak/STAT pathway activation will be determined in both epithelial and fibroblast cell cultures. Pathway analysis will be performed using commercially available proteome array and their activation validated by western blot.

Suitable For ☒ Honours ☒MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Bachelor of Science or equivalent.

• Good written and oral communication skills;

• Motivation and organisational skills;

• Able to work as part of a team. Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: A/Professor Cecilia Prêle (08) 6151 0958 [email protected]

36

Personalised CFTR Therapy Screening using a Genetically Modified, Primary Airway Epithelial Cell Based High‐Throughput Screening Assay Research Program Respiratory Health Research Group Airway Epithelial Research Start Date February 2020 Chief Supervisor Dr Luke Garratt (Telethon Kids Institute, The University of Western Australia) Other Supervisors Dr Erika Sutanto (Telethon Kids Institute)

Dr Colette Moses (Telethon Kids Institute) A/Professor Anthony Kicic (Telethon Kids Institute, The University of Western Australia, Curtin University) Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

Project Outline Cystic fibrosis (CF) is a genetically inherited disease affecting >30,000 people worldwide. CF is caused by mutations in the CFTR gene which result in defective protein function, driving pathology in multiple organs. It is now possible to correct mutations with specific small molecules addressing CFTR mutation consequences. However, with >1700 mutations there is a critical need for models which can report CFTR function for high throughput screening (HTS) of potential drugs. We developed technology to continually grow primary airway cells from people with CF in the laboratory and make them produce a fluorescent marker for CFTR function. However, we found airway cells only express very low amounts of CFTR when growing in formats suitable for HTS, limiting the assay potential. The primary aim of this project is to make non-CF and CF primary airway cells overexpress their specific CFTR proteins (including any mutations) by inducing endogeneous CFTR expression through CRISPR/dCas9. It will validate the use of the high throughput screening assay in screening compounds for CF, by comparing this assay against gold standard using chamber and rectal organoid models we have established. Once validated, the project will refine the processes involved to streamline application in drug development partnerships and future clinical applications. A secondary aim will be to characterise the ability of dCas9 expressing primary airway cells to differentiate in vitro and form pseudostratified airway epithelium in the laboratory. This will create a novel model through which the function and consequence of any gene of interest to respiratory disease could be explored.



• Understanding of genetics and genetically modified organisms


• Motivation and organisational skills

• Ability to work as part of a team Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Luke Garratt (08) 6319 1804 [email protected]

37

Screening Amniotic Epithelium Research Program Respiratory Health Research Group Airway Epithelial Research Start Date January 2020 Chief Supervisor Dr Thomas Iosifidis (Telethon Kids Institute) Other Supervisors Professor Jeffrey Keelan (The University of Western Australia)

Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital) A/Professor Anthony Kicic (Telethon Kids Institute, The University of Western Australia, Curtin University)

Project Outline Chronic respiratory diseases are a major healthcare burden in Australia with disease development originally thought to start in later life. We now understand that the early life environment, and even conditions during pregnancy such as maternal asthma severity, play an important role in determining risk to develop poor respiratory outcomes, such as wheeze and asthma in the offspring. Studies by our team on the airway epithelium from infants and children have led us to the hypothesis that a “vulnerable epithelium” endotype can contribute to poor clinical respiratory health, such as wheeze and asthma. Importantly, the prenatal environment has been postulated as a key modulator of epithelial vulnerability. Interestingly, altered epithelial endotypes have been identified in fetal origin epithelial tissues such as amniotic epithelium and characterised by markers of inflammation and impaired repair capacity. It remains to be determined if the amniotic epithelium of infants born to asthmatic mothers displays hallmarks of the vulnerable epithelium, such as inflammation and defective repair, compared to non-asthmatic counterparts. This project aims to isolate amniotic epithelial cells and determine if there are intrinsic differences between the amniotic epithelium from births to mothers with asthma compared to non-asthmatic mothers. This will be done by accessing placenta from the ORIGINS birth cohort. The first aim of the project will be to process amniotic membranes from placentas and isolate amniotic epithelial cells. The second aim will be to characterise the cells present in the amniotic epithelium using Flow cytometry and immunocytochemical staining protocols. Finally, the third aim of the project will be to culture amniotic epithelial cells and assess cell morphology, proliferation, repair rates and production of inflammatory cytokines. This will be the first study to assess the amniotic epithelium of infants born to asthmatic mothers and may provide a potential mechanism explaining how exposures during pregnancy affect vulnerability in the offspring.




• Ability to work with clinical samples Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Thomas Iosifidis (08) 6319 1807 [email protected]

38

Associations between Disease Progression and Quality of Life in Children with Neuromuscular Disorders Research Program Respiratory Health Research Group Children’s Lung Health Start Date March 2020 Chief Supervisor A/Professor Jenny Downs (Telethon Kids Institute) Other Supervisors Professor Graham Hall (Telethon Kids Institute, Curtin University)

Dr Andrew Wilson (Telethon Kids Institute, Perth Children’s Hospital) Dr Adelaide Withers (Telethon Kids Institute, Perth Children’s Hospital)

Project Outline Neuromuscular conditions affect people of all ages with the incidence estimated to be approximately 1 in 3000. Respiratory failure is the leading cause of morbidity and death due to impaired gas exchange (hypoventilation). High respiratory morbidity is accompanied by other challenges to daily wellbeing and quality of life afforded by poor sleep, fatigue and poor mental health. This project will investigate physical health, well-being and quality of life over time in children with neuromuscular conditions. Data will be collected longitudinally to understand trajectories of physical and mental health as well as quality of life, and predictors of membership to the trajectory classes. Qualitative interview data will also be collected to explore lived experiences in greater detail, to cross reference with the structure of available patient-reported outcome measures, and to inform quality of life when living with a serious health condition. This study is embedded within a larger collaboration with Stanford University and the Lucille Packard Children’s Hospital in California, and there is potential to collaborate and visit in conducting this PhD. Components of the study could suit Honours or Masters study.


• Well-developed interpersonal and communication skills

• Ability to work in a multidisciplinary team

• Motivated and dedicated

• Good organisational skills

• Able to work as part of a team Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: A/Professor Jenny Downs 0411 161 138 [email protected]

39

Can a Short Trial of Flixotide in Children with Airway Inflammation Improve Outcomes after ENT Surgery? Research Program Respiratory Health Research Group Children’s Lung Health Start Date February 2020 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Elizabeth Smith (Telethon Kids Institute) Project Outline The rate of postoperative complications in children undergoing tonsillectomy is high, with

up to 48% of children experiencing an adverse respiratory event. Preliminary data from our group has shown that airway inflammation may play a pivotal role in this story. A small pilot study of children with respiratory symptoms found that 70% of children with airway inflammation experienced respiratory complications compared with only 10% of children who did not. Airway inflammation can be assessed non-invasively through the measurement of exhaled nitric oxide, however the current pre-operative risk assessment does not include this measure. Our group is undertaking a trial to assess whether pre-operative treatment with an anti-inflammatory medication (inhaled corticosteroids) can decrease the incidence of respiratory complications in children with respiratory symptoms and active airway inflammation. As part of this project you will be based at Telethon Kids Institute in Perth Children’s Hospital, and will accompany the research team to Ear, Nose and Throat (ENT) clinics and day surgery wards across the city. Your role within this team will include:

• Meeting families undergoing ENT surgery and screening for trial eligibility

• Basic lung function testing (FeNO)

• Interviewing parents for post-surgery follow ups

• Database management

• Data analysis You will be part of a lively, cohesive team motivated to improve the lung health of children in Australia and worldwide. The data analysis you perform will constitute the interim analysis for the project and contribute to the work of this team.



• Highly motivated and organised

• Excellent interpersonal skills, including an ability to interact with children and their families.


☐ Full scholarship offered by project group For more information, please contact: Dr Elizabeth Smith (08) 6319 1178 [email protected]

40

Developing Clinical Predictors of Disease Progression in Children with Neuromuscular Disorders to Prevent Future Respiratory Failure Research Program Respiratory Health Research Group Children’s Lung Health Start Date March 2020 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Andrew Wilson (Telethon Kids Institute, Perth Children’s Hospital)

Dr Adelaide Withers (Telethon Kids Institute, Perth Children’s Hospital) Project Outline Neuromuscular conditions affect people of all ages with the incidence estimated to be

approximately 1 in 3000. Respiratory failure is the leading cause of morbidity and death due to impaired gas exchange (hypoventilation). Currently, the techniques to measure respiratory function can involve forced respiratory manoeuvres which can be difficult to perform in children with neuromuscular disease. The gold standard for diagnosis of hypoventilation in children with neuromuscular disease is a sleep study (polysomnography). The new Ventica system allows for reliable testing of paediatric lung function during sleep for subsequent analysis of signs of asthma. This project will examine whether the Ventica system could be used to assess respiratory function in children with neuromuscular disease. Data will be collected and analysed to investigate whether the device can be used during in-laboratory polysomnography in children above 5 years of age with neuromuscular disease. The outcome of this study will be to evaluate and determine the usefulness of the Ventica system in a different cohort.



• Able to work as part of a team


• This project would suit a student with a sleep physiology background Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Professor Graham Hall (08) 6319 1594 [email protected]

41

Developing Clinical Predictors of Disease Progression in Children with Neuromuscular Disorders to Prevent Future Respiratory Failure Research Program Respiratory Health Research Group Children’s Lung Health Start Date March 2020 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors A/Professor Jenny Downs (Telethon Kids Institute)

Dr Jenny Lam (Telethon Kids Institute) Dr Andrew Wilson (Telethon Kids Institute, Perth Children’s Hospital) Dr Adelaide Withers (Telethon Kids Institute, Perth Children’s Hospital)

Project Outline Neuromuscular conditions affect people of all ages with the incidence estimated to be approximately 1 in 3000. Respiratory failure is the leading cause of morbidity and death due to impaired gas exchange (hypoventilation). Despite knowledge that hypoventilation is associated with high respiratory morbidity, and that respiratory failure is the leading cause of morbidity and death in this group of patients, identifying hypoventilation can be problematic. This is because symptoms can be non-specific, misleading and easily misunderstood with symptoms of the underlying condition. With a combination of clinical features and pulmonary function testing, it is likely these measures will be the most predictive of the onset of hypoventilation. Working in collaboration with Stanford University and the Lucile Packard Children’s Hospital in California, USA, this project will provide insight for the onset of hypoventilation in children and adolescents with neuromuscular conditions. Outcomes from this study will help us better understand the most accurate method of determining when the onset of hypoventilation has occurred in asymptomatic children.




• Highly motivated and organised Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Jenny Lam (08) 6319 1854 [email protected]

42

Exploring the Effects of Preterm Birth on the Airway Epithelium Research Program Chronic & Severe Diseases Research Group Children’s Lung Health

Airway Epithelial Research Start Date Early 2019 Chief Supervisor A/Professor Anthony Kicic (Telethon Kids Institute, Curtin University, The University of

Western Australia) Other Supervisors Dr Shannon Simpson (Telethon Kids Institute, Curtin University)

Dr Kevin Looi (Telethon Kids Institute) Project Outline On a global scale, over 2 million babies are delivered very preterm (<32 weeks gestation)

every year. Many of these infants display significant respiratory symptoms that persist throughout childhood, a result of being born before lung development is complete. The long-term consequences of interrupted lung development are not well understood, particularly for the airway epithelium. The airway epithelium lines the respiratory tract to create a protective barrier from foreign pathogens, such as bacteria, and plays an essential role in the state of health or disease. Given the persistent respiratory symptoms and interrupted development associated with preterm birth, we believe that abnormalities exist in the airway epithelium of children born prematurely. To investigate this hypothesis, we have successfully established a primary cell culture model of the preterm airway epithelium. There is now an opportunity for motivated students to help us explore and understand the consequences of preterm birth on the airway epithelium using a variety of downstream analytical techniques. Techniques involved may include, but are not limited to: primary cell culture using stringent aseptic technique, ELISAs, protein extraction, gene expression analysis and immunocytochemistry.

Suitable For ☐ Honours ☐ MD ☐ Masters ☒ PhD Essential Skills & Qualifications

• Excellent oral and written communication skills


• Highly motivated and organised Ethics Approval ☐ Obtained ☒ Not Obtained (pending) Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Shannon Simpson (08) 6319 1361 [email protected]

43

Forced Oscillation Technique: Clinical Utility of Within-Breath Analysis

Research Program Chronic & Severe Diseases Research Group Children’s Lung Health Start Date Early 2019 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Shannon Simpson (Telethon Kids Institute, Curtin University) Project Outline The forced oscillation technique (FOT) utilises soundwaves to study the structural and

mechanical properties of the lungs. The test is non-invasive and requires minimal patient cooperation, making it ideal for use in pre-schoolers and young children. However, routine integration of FOT into clinical practice has been slowed by a lack of clear guidelines and uncertainty regarding the relevant reportable outcomes. The traditional method for reporting FOT outcomes has been to record the data over several breaths and report a single value encompassing both the inspiratory and expiratory components of breathing. However, it is possible that analysing the inspiratory and expiratory components separately could provide valuable information about the airway, which may be helpful in the clinical monitoring of paediatric lung disease. This project will therefore provide a student the opportunity to examine the clinical relevance of separating the inspiratory and expiratory components of FOT data. Data will be collected across multiple paediatric respiratory conditions, including cystic fibrosis, asthma, neuromuscular disease and chronic lung disease of prematurity.


• Excellent oral and written communication skills


• Highly motivated and organised Ethics Approval ☒ Obtained ☐ Not Obtained (pending) Funding ☐ Top-up scholarship offered by project group


44

Global Lung Function Initiative (GLI): Deriving Global Multi-Ethnic Reference Values for the Measurement of Lung Function Research Program Chronic & Severe Diseases Research Group Children’s Lung Health Start Date January 2020 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Sanja Stanojevic (The Hospital for Sick Children, Toronto) Project Outline Background: Pulmonary Function Tests (PFT) are important for assessing the health of the

lungs and for medical diagnoses of respiratory and related diseases. Interpretation of these tests rely on the availability of appropriate reference data to distinguish between health and disease and to assess the severity and nature of any functional impairment. However, there is no consensus on suitable reference data for many common PFTs and default reference equations commonly used in clinics may not be suitable across the entire age range or in non-Caucasian populations. Objectives: The Global Lung Function Initiative (GLI) is a collaboration of international clinicians and researchers with an overall objective to establish improved, multi-ethnic, all–age, lung function reference data that are representative of the population or individuals under study irrespective of their age, ethnic group or equipment used. The GLI has been successful in developing all-age, multi-ethnic reference equations for spirometry - the most common PFT, carbon monoxide transfer factor for Caucasians and currently collecting data for lung volumes reference equations. This project presents an opportunity to participate in retrospective or prospective GLI studies to develop similar reference equations in other ethnic groups (especially in Asia and Sub Saharan Africa populations) and for other commonly used PFTs. Reference equations will be generated and disseminated for use by researchers, clinicians and equipment manufacturers. Method: The GLI requests for anonymized data from individuals, groups or manufacturers who have collected PFT data from healthy population and that meets established GLI criteria. For example, the data must have been collected on a minimum of 100 participants, must contain essential background information for each subject (age, sex, height, ethnic group, health status, etc), and appropriate consent must have been sought for data collection and sharing. The collated data is then analysed using established statistical analysis used by the GLI.



• Able to work as part of a multidisciplinary team


• The opportunity will be highly suited to students with a background in Respiratory physiology, Biostatistics, Epidemiology or Public Health



45

Imaging the Long-Term Effects of Preterm Birth on the Lung Research Program Respiratory Health Research Group Children’s Lung Health Start Date Flexible Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Tim Rosenow (Telethon Kids Institute)

Dr Shannon Simpson (Telethon Kids Institute, Curtin University) Dr Andrew Wilson (Telethon Kids Institute, Perth Children’s Hospital) Professor Harm Tiddens (Sophia Children’s Hospital [Netherlands])

Project Outline Preterm birth leads to a range of health consequences, with chronic lung disease being the most common. Despite this, little is known about the long-term effects of prematurity on the lung. Children who were born preterm have a high rate of respiratory morbidity, but often have little to no clinical follow-up after infancy. Earlier work in the West Australian Lung Health In Prematurity (WALHIP) study suggests that there are significant structural lung abnormalities present in children born preterm, and that these are associated with ongoing respiratory symptoms. With the advent of advanced lung imaging techniques such as low-dose computed tomography (CT) and magnetic resonance imaging (MRI), we can now assess in detail the structure and function of the lung. We will use these techniques to follow up the WALHIP cohort, now in early adulthood, to determine if there is still significant ongoing structural lung disease. For this project, you will be responsible for retrieving and analysing these scans, for comparison against a range of clinical and physiological measures. You will additionally compare their scans to that of a healthy control group. By characterising the lung disease seen in this cohort, we can develop new ways to treat and monitor the respiratory health of children and adults who were born preterm. As part of this project, there is the opportunity to spend up to 12 months in Rotterdam, The Netherlands with our collaborator, Professor Harm Tiddens at the Sophia Children’s Hospital. Here you will learn how to analyse CT and MRI scans and interpret them in a clinical context.


• Undergraduate degree in physiology, medical or health science, biomedical engineering, or biophysics

• Eligibility for enrolment into a PhD programme Ethics Approval ☐ Obtained ☒ Not Obtained (pending) Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group For more information, please contact: Dr Tim Rosenow (08) 6319 1633 [email protected]

46

Personalised, Machine Learning Based Prediction of Asthma and Allergies in Western Australia Research Program Respiratory Health Research Group Children’s Lung Health Start Date July 2019 Chief Supervisor Dr Rachel Foong (Telethon Kids Institute, Curtin University) Other Supervisors Dr Sebastian Rauschert (Telethon Kids Institute)

Professor David Broadhurst (Edith Cowan University) Mr Paul Stevenson (Telethon Kids Institute)

Project Outline Asthma is the most common chronic lung disease of childhood. In Western Australia, nearly 9% of children report having a doctor diagnosis of asthma. Asthma diagnosis is difficult in young children. Therefore, there has been a worldwide effort to develop ways to identify asthma risk as early as possible in order to prevent disease. This project aims to show that asthma and allergies in individuals can be predicted before it occurs based on individual family history and information on the early environment. The aim is to create personalized prediction scores for the development of asthma and allergy by using machine learning, which will help in better understanding, preventing and managing asthma. The Raine Study will be utilised to develop the prediction scores. For this study over 2800 pregnant women were recruited in Perth, WA and asthma and allergies have been well-studied in this cohort at 5/6-years, 13/14-years and 22/23-years in children. In addition to questionnaire data, the Raine study has lung function and immunological measurements from participants which can be used to generate prediction scores. Furthermore, genetic and epigenetic data is available for more than 1000 study participants, which may be assessed in relation to the predictive modelling. Once prediction scores have been developed, the findings will be validated in other birth cohorts within Australia and within international birth cohort studies. The findings from this study will identify risk factors in early life for asthma and allergies. In the era of personalized medicine, the ability to undertake an individualized risk assessment based on familial history and past exposures may present an attractive means for targeted approaches for early intervention and prevention. Furthermore, a predictive model of asthma and allergies based on questionnaire data and family history may help doctors make decisions quickly in a cost-efficient way. It can improve diagnosis of asthma and allergy and can be helpful in disease management.


• Have an Honours degree or equivalent in statistics or other data analysis qualifications

• Eligible to enrol in a PhD at a University

• Self-management and high personal motivation

• Excellent communication and interpersonal skills

• Knowledge of a programming language (preferably R, Python or related data analysis and machine learning tools)

• Some experience with the UNIX computational environment and/or cloud computing

Ethics Approval ☐ Obtained ☒ Not Obtained Funding ☐ Top-up scholarship offered by project group

☒ Full scholarship offered by project group For more information, please contact: Dr Rachel Foong (08) 6319 1626 [email protected]

47

Predicting Long-Term Health Outcomes in Young Adults Born Very Preterm (WALHIP 19-Year Follow-Up) Research Program Respiratory Health Research Group Children’s Lung Health Start Date February 2019 Chief Supervisor Professor Graham Hall (Telethon Kids Institute, Curtin University) Other Supervisors Dr Shannon Simpson (Telethon Kids Institute, Curtin University)

Dr Andrew Wilson (Telethon Kids Institute, Perth Children’s Hospital, The University of Western Australia, Curtin University)

Project Outline Nearly 11% of global births are preterm, with the largest health burden in those born <32 weeks gestational age. Bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease, is the most common chronic condition in preterm infants. Significant improvements in neonatal care have profoundly changed the clinical and pathological characteristics of very preterm infants and BPD, such that the term “new” BPD has been coined. Survivors of very preterm birth (irrespective of BPD status) go on to have a high burden of lung disease with cross-sectional studies reporting reduced lung function, increased respiratory symptoms and structural lung damage. There are only limited longitudinal respiratory health studies that have followed preterm individuals throughout childhood and into early adult life. As such, the natural history and outcomes of these individuals into adulthood are largely unknown. Our earlier work following the West Australian Lung Health in Prematurity (WALHIP) cohort has suggested that preterm children have increased respiratory symptoms and declining lung function. Our primary objective, therefore, is to identify the respiratory outcomes that persist into early adulthood in a 19-year follow-up of the WALHIP cohort both with and without BPD and establish a baseline for the continuing study of chronic lung disease in later life in individuals born preterm. This objective will be achieved by:

• Undertaking a comprehensive respiratory assessment

• Identifying within the 6 and 11-year follow-up data, the characteristics which predict the persistence and/or progression of respiratory morbidity to 19 years of age.

The transition between the child and adult forms of chronic lung disease is a crucial research issue and this NHMRC funded project offers a range of opportunities to students.


• Above average oral and written communication skills

• Motivation and organisation skills

• Able to work as part of a team Ethics Approval ☐ Obtained ☒ Not Obtained (pending) Funding ☐ Top-up scholarship offered by project group


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Understanding Asthma and Respiratory Health in Urban and Regional Areas of Western Australia Research Program Respiratory Health Research Group Children’s Lung Health Start Date August 2019 Chief Supervisor Dr Rachel Foong (Telethon Kids Institute, Curtin University) Other Supervisors Professor Graham Hall (Telethon Kids Institute, Curtin University) Project Outline Asthma is a significant health problem affecting one in ten Australians. Studies show that

asthma rates in Aboriginal and Torres Strait Islander Australians are double that of non-Aboriginal Australians. Additionally, Aboriginal people in non-remote areas such as major cities are twice as likely as to have asthma compared to those living in remote areas. However, information on how many people have asthma is still lacking in different regions throughout Australia and information on the actual burden of disease is largely unknown. As such, there is a need for community studies to identify the burden of disease to enable improved approaches for managing and treating asthma. The Global Asthma Network (GAN) is an international study aiming to prevent asthma and improve care globally. GAN provides validated questionnaires that examine the prevalence and severity of asthma, and explores asthma diagnosis, management and environmental risk factors. We are currently undertaking GAN in the Perth metropolitan area, however given there is paucity of accurate prevalence data on respiratory disease in regional areas throughout Australia, there is a need for resources to be developed as to improve prevention, diagnosis and treatment of lung disease within these regions. In the Kimberley region, where 46% of the population is Aboriginal, asthma was the 4th most commonly self-reported, doctor-diagnosed chronic disease in adults and there is evidence to suggest that in children, other chronic respiratory diseases such as bronchiectasis, chronic suppurative lung disease and recurrent protracted bacterial bronchitis may be misdiagnosed as asthma. Therefore, the GAN protocol will need to be adapted to include questions on other chronic diseases and environmental exposures following a consultation process. The overarching objective of this project is to be able to adapt the GAN model into a culturally appropriate tool to allow for a better understanding of asthma and chronic respiratory disease prevalence and management in urban and regional WA. The PhD student will engage in close consultation with community members, utilising participatory action research methods to develop a culturally appropriate GAN protocol and work to implement this protocol. Based on the information derived from the study, the student will work with community members to ensure effective translation into improved health outcomes.


• Have an Honours degree or equivalent

• Eligible to enrol in a PhD at a University

• Excellent communication and interpersonal skills

• Self-management and high personal motivation

• Experience with engagement of Aboriginal community members

• Demonstrated capacity to work with families, children and young people.

• Complete regular travel to the Kimberley (Broome) Ethics Approval ☒ Obtained ☐ Not Obtained Funding ☐ Top-up scholarship offered by project group

☒ Full scholarship offered by project group For more information, please contact: Dr Rachel Foong (08) 6319 1626 [email protected]

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Aetiology of Childhood Acute Asthma Research Program Respiratory Health Research Group Children’s Respiratory Science Group Start Date March 2020 Chief Supervisor Dr Ingrid Laing (Telethon Kids Institute, The University of Western Australia) Other Supervisors Professor Peter Le Souëf (The University of Western Australia)

A/Professor Guicheng Zhang (Curtin University) Project Outline BACKGROUND: Asthma is one of the most common reasons children need emergency

medical treatment in Western Australia. Our research program involves studying young children during the peak of their acute asthma attack. Studying children at this time with a follow-up on recovery is the best way to discover the underlying causes of asthma. We also compare results to those of healthy children, so we can understand just how stressed the systems are during acute asthma and how much they recover afterwards. We also characterise each child’s clinical status including their lifetime history of recurrent exacerbations to identify their tendency to develop persistent asthma. We have a number of projects using different technologies to study the mechanisms of asthma:

• Persistence of type 1 interferon signatures in children with acute asthma

• Stability of metabolomic signatures that predict disease persistence

• Respiratory viral responses of in vitro epithelial cells AIM OF THE PROJECT: The aim is to elucidate the biological mechanisms that contribute to the susceptibility to, and severity of wheezing and asthma exacerbations in children. Projects are available in each of our areas of research and we would be pleased to discuss tailoring a project to a student’s area of interest. METHODOLOGY and STUDENT EXPERIENCE: Each project is likely to use a variety of the latest laboratory and analysis techniques to further the applicants’ skills. Students may also have the opportunity to gain experience with recruitment and follow-up of children and with sample processing if appropriate.

Suitable For ☐ Honours ☒ MD ☒ Masters ☒ PhD Essential Skills & Qualifications

• Undergraduate degree in science

• Excellent communication and team participation skills

• Proficient writing and presentation skills

• If relevant to the proposed project – laboratory experience and/or proficiency in statistical analysis


☐ Full scholarship offered by project group For more information, please contact: Dr Ingrid Laing (08) 6319 1828 or 0405 352 952 [email protected]

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Advanced Analysis of CT Scans of Lung Disease Research Program Respiratory Health

Research Group P4 Respiratory Health for Kids Children’s Lung Health Respiratory Environmental Health

Start Date Flexible

Chief Supervisor A/Professor Peter Noble (The University of Western Australia)

Other Supervisors Dr Tim Rosenow (Telethon Kids Institute) Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital) Professor Alan James (Sir Charles Gairdner Hospital)

Project Outline Medical imaging technologies such as Computed Tomography (CT) scans are critical tools for the diagnosis and management of lung disease. However, current methods of analysis and reporting of CT scans are crude, lacking objectivity and reproducibility. Advanced techniques in development have the potential to provide more sensitive and accurate outcome measures but need further optimisation and testing in patient groups before they can become part of routine clinical use. In this project, you will use a number of newly developed image analysis techniques to compare CT scan outcomes between patients across several clinical cohorts. These techniques include both automated and manual 3D analysis of scans taken from children and adults with a range of diseases, including cystic fibrosis, bronchopulmonary dysplasia (preterm birth), COPD, and asthma. The results from this project will be used to develop new tools for use in the clinic.

Suitable For ☒ Honours ☐ MD ☒ Masters ☒ PhD

Essential Skills & Qualifications

• Undergraduate degree in physiology, medical or health science, biomedical engineering, or biomedical physics

Ethics Approval ☒ Obtained ☐ Not Obtained

Funding ☐ Top-up scholarship offered by project group

☐ Full scholarship offered by project group

For more information, please contact:

Dr Tim Rosenow (08) 6319 1633 [email protected]

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Artificial Intelligence to Diagnose Lung Infection and Provide Prognosis on CT Scans in Cystic Fibrosis Research Program Respiratory Health

Research Group P4 Respiratory Health for Kids

Start Date Flexible

Chief Supervisor Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

Other Supervisors Dr Tim Rosenow (Telethon Kids Institute) Dr Yuliya Karpievitch (Telethon Kids Institute)

Project Outline Cystic fibrosis (CF) is a genetic disorder that causes progressive fatal lung disease. One of the key drivers of lung disease progression is pulmonary infection. In young children, reliable diagnosis of infection requires the use of invasive procedures such as bronchoscopy. Computed tomography (CT) scanning is a quick, non-invasive and inexpensive method to detect structural disease in the lung. Although CT is widely used in the management of CF and is the most sensitive method to detect lung disease, it has not been used specifically to identify lung infection. It is likely that specific pathogens, such as Pseudomonas aeruginosa and Aspergillus sp., have different effects on the lung and thus will present differently on CT. Artificial intelligence/machine learning is an ideal approach to identifying infection-specific attributes of structural lung disease and developing an automated software for infection screening and prognosis and treatment suggestions. In this project, you will work with AREST CF: an integrated clinical and scientific team with a strong international reputation as leaders in paediatric CF research. The aim of this project is to use cutting edge machine learning techniques to develop an automated screening tool for lung infection, based on the databank of more than 1000 CT scans of young children with CF. Not only will this project create a rapid, automated identification of patients at risk of infection, you will be using the results to identify infection-specific CT abnormalities, which will be used to guide clinical management.

Suitable For ☐ Honours ☐ MD ☐ Masters ☒ PhD


• Undergraduate degree in physiology, medical or health science, biomedical engineering, biostatistics, data science, or biophysics

• Eligibility for enrolment into a PhD programme






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Automated Tracking of Epithelial Cell Migration Research Program Respiratory Health


Start Date Flexible

Chief Supervisor A/Professor Anthony Kicic (Telethon Kids Institute, The University of Western Australia, Curtin University)

Other Supervisors Dr Thomas Iosifidis (Telethon Kids Institute) Dr Tim Rosenow (Telethon Kids Institute) Dr Yuliya Karpievitch (Telethon Kids Institute)

Project Outline Repair of the lung epithelium following injury is critical to maintaining airway structure and satisfactory respiratory function. Wound repair dysfunction is a key contributor to a number of respiratory diseases, including asthma. In vitro modelling of an epithelial layer following mechanical injury has shown that impaired wound repair is in part caused by disordered cell migration. Tracking of epithelial cells near the wound edge has led to important discoveries about the mechanisms involved in wound repair in health and disease. However, analysis of cell migration involves manual selection and labelling of individual cells and is thus a labour- and time-intensive task that is prone to observer bias. Automated cell tracking is essential to producing high quality analysis in large volume. In this project, you will work with leading researchers in airway epithelial research to develop artificial intelligence-based cell tracking software. You will be using state of the art image recognition tools to design, develop and validate a method to identify and track individual cells, characterise their trajectory, and use these data to investigate wound repair mechanisms across a range of childhood lung diseases. This project has the potential to develop a commercial cell-tracking software product.

Suitable For ☐ Honours ☐ MD ☒ Masters ☒ PhD


• Undergraduate degree in physiology, biomedical engineering, biostatistics, data science, or biophysics.

• Computer programming expertise • Eligibility for enrolment into a PhD programme






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Validation of Lung MRI as a Clinical Endpoint in Cystic Fibrosis Research Program Respiratory Health


Start Date Flexible

Chief Supervisor Professor Stephen Stick (Telethon Kids Institute, Perth Children’s Hospital)

Other Supervisors Dr Tim Rosenow (Telethon Kids Institute) Professor Harm Tiddens (Sophia Children’s Hospital [Netherlands])

Project Outline Cystic fibrosis (CF) is a genetic disorder that that causes progressive, fatal lung disease. The primary manifestation of this is structural lung damage, which is best diagnosed and monitored using computed tomography (CT). However, because CT uses ionising radiation it cannot be performed frequently, making it unsuitable for short-term monitoring of disease progression. This is particularly problematic when treating pulmonary exacerbations – short periods involving a rapid increase in symptoms and an acceleration of lung disease, generally due to lung infection. Magnetic resonance imaging (MRI) is a radiation-free alternative to CT that has recently gained traction as a means to detect CF-related structural lung damage. Although promising, little validation has been performed on its sensitivity to detect the subtle abnormalities seen in children. In this project, you will work within AREST CF: an integrated clinical and scientific team with a strong international reputation as leaders in paediatric CF research. You will be involved in the DEFEND-CF study, collecting lung CT, MRI, and a number of clinical and research measures in children with CF during, before, and after a pulmonary exacerbation. The aim of this project is to compare the sensitivity of MRI to detect lung disease in comparison to the gold standard (CT), and to determine whether MRI can be used to monitor changes to lung disease status during a pulmonary exacerbation and following treatment. As part of this project, there is the opportunity to spend up to 12 months in Rotterdam, The Netherlands with our collaborator, Professor Harm Tiddens at the Sophia Children’s Hospital. Here you will learn how to analyse CT and MRI scans and interpret them in a clinical context.

Suitable For ☐ Honours ☐ MD ☐ Masters ☒ PhD


• Undergraduate degree in physiology, medical or health science, biomedical engineering, or biophysics

• Eligibility for enrolment into a PhD programme






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